Fused-ring compounds and use thereof as drugs

ABSTRACT

The present invention provides a fused ring compound of the following formula [I] 
                 
wherein each symbol is as defined in the specification, a pharmaceutically acceptable salt thereof, and a therapeutic agent for hepatitis C, which contains this compound. The compound of the present invention shows an anti-hapatitis C virus (HCV) action based on the HCV polymerase inhibitory activity, and is useful as a therapeutic agent or prophylactic agent for hepatitis C.

This is a continuation in part of U.S. patent application Ser. No.09/939,374 filed on Aug. 24, 2001, which is a continuation in part ofPCT/JP00/09181 filed on Dec. 22, 2000.

TECHNICAL FIELD

The present invention relates to a novel fused ring compound and apharmaceutically acceptable salt thereof useful as a therapeutic agentfor hepatitis C, and to an intermediate compound for the synthesisthereof. The present invention also relates to a novel use of a certainfused ring compound or a pharmaceutically acceptable salt thereof as atherapeutic agent for hepatitis C. More particularly, the presentinvention relates to a therapeutic agent for hepatitis C, which containsa novel fused ring compound or a pharmaceutically acceptable saltthereof, which is effective for the prophylaxis or treatment ofhepatitis C and which shows anti-hepatitis C virus (HCV) activity,particularly anti-HCV activity based on an RNA-dependent RNA polymeraseinhibitory activity.

BACKGROUND ART

In 1989, a main causative virus of non-A non-B posttransfusion hepatitiswas found and named hepatitis C virus (HCV). Since then, several typesof hepatitis viruses have been found besides type A, type B and type C,wherein hepatitis caused by HCV is called hepatitis C.

The patients infected with HCV are considered to involve several percentof the world population, and the infection with HCV characteristicallybecomes chronic.

HCV is an envelope RNA virus, wherein the genome is a single strandplus-strand RNA, and belongs to the genus Hepacivirus of Flavivirus(from The International Committee on Taxonomy of Viruses, InternationalUnion of Microbiological Societies). Of the same hepatitis viruses, forexample, hepatitis B virus (HBV), which is a DNA virus, is eliminated bythe immune system and the infection with this virus ends in an acuteinfection except for neonates and infants having yet immatureimmunological competence. In contrast, HCV somehow avoids the immunesystem of the host due to an unknown mechanism. Once infected with thisvirus, even an adult having a mature immune system frequently developspersistent infection.

When chronic hepatitis is associated with the persistent infection withHCV, it advances to cirrhosis or hepatic cancer in a high rate.Enucleation of tumor by operation does not help much, because thepatient often develops recurrent hepatic cancer due to the sequelainflammation in non-cancerous parts. In addition, there is a report onthe involvement of HCV infection in dermatosis such as chronicurticaria, lichen planus, cryoglobulinemic purpura and the like (TheJapanese Journal of Dermatology, 111(7), 1075-81, 2001).

Thus, an effective therapeutic method of hepatitis C is desired. Apartfrom the symptomatic therapy to suppress inflammation with ananti-inflammatory agent, the development of a therapeutic agent thatreduces HCV to a low level free from inflammation and that eradicatesHCV has been strongly demanded.

At present, a treatment with interferon is the only effective methodknown for the eradication of HCV. However, interferon can eradicate thevirus only in about one-third of the patient population. For the rest ofthe patients, it has no effect or provides only a temporary effect.Therefore, an anti-HCV drug to be used in the place of or concurrentlywith interferon is awaited in great expectation.

In recent years, Ribavirin(1-β-D-ribofuranosyl-1H-1,2,4-triazole-3-carboxamide) has becomecommercially available as a therapeutic agent for hepatitis C, which isto be used concurrently with interferon. It enhances the efficacy ofinterferon but only to a low efficacy rate, and a different noveltherapeutic agent for hepatitis C is desired.

Also, an attempt has been made to potentiate the immunocompetence of thepatient with an interferon agonist, an interleukin-12 agonist and thelike, thereby to eradicate the virus, but an effective pharmaceuticalagent has not been found yet.

In addition, the inhibition of HCV growth, wherein HCV-specific proteinis targeted, has been drawing attention these days.

The gene of HCV encodes a protein such as serine protease, RNA helicase,RNA-dependent RNA polymerase and the like. These proteins function as aspecific protein essential for the growth of HCV.

One of the specific proteins, RNA-dependent RNA polymerase (hereinafterto be also briefly referred to as an HCV polymerase), is an enzymeessential for the growth of the virus. The gene replication of HCVhaving a plus-strand RNA gene is considered to involve synthesis of acomplementary minus-strand RNA by the use of the plus-strand RNA as atemplate, and, using the obtained minus-strand RNA as a template,amplifying the plus-strand RNA. The portion called NS5B of a proteinprecursor, that HCV codes for, has been found to show an RNA-dependentRNA polymerase activity (EMBO J., 15, 12-22, 1996), and is considered toplay a central role in the HCV gene replication.

Therefore, an HCV polymerase inhibitor can be a target in thedevelopment of an anti-HCV drug, and the development thereof is eagerlyawaited. However, an effective HCV polymerase inhibitor has not beendeveloped yet, like in other attempts to develop an anti-HCV drug basedon other action mechanisms. As the situation stands, no pharmaceuticalagent can treat hepatitis C satisfactorily.

The following discloses known compounds relatively similar to thecompound of the present invention.

The therapeutic agents for hepatitis C, which have a benzimidazoleskeleton, are known from JP-A-2001-247550 (WO01/47883, EP1162196A1) andWO02/04425.

These publications disclose the following β-ketoamide compounds J etc.and K etc., respectively, as anti-HIV agents having an integraseinhibitory activity:

Note that the earliest publication dates of these publications are Jul.5, 2001 (WO01/47883) and Jan. 17, 2002 (WO02/04425), and the prioritydate of the present application is Jun. 26, 2001, antedating thesepublication dates.

In addition, a known therapeutic agent for hepatitis C having abenzimidazole skeleton is also disclosed in WO97/36866, Japanese PatentApplication under PCT laid-open under kohyo No. 2000-511899 (EP906097)and WO99/51619.

WO97/36866 discloses the following compound D and the like, and HCVhelicase inhibitory activity of the compounds.

Japanese Patent Application under PCT laid-open under kohyo No.2000-511899 (EP906097) discloses the following compound E and the like,and WO99/51619 discloses the following compound F and the like, in bothof which a possibility of these compounds being effective as an HCVinhibitor is mentioned.

However, these publications do not include the compound disclosed in thepresent specification, or a disclosure suggestive thereof.

A known anti-hepatitis virus agent having a benzimidazole skeleton isdisclosed in Japanese Patent Application under PCT laid-open under kohyoNo. 2000-503017 (WO97/25316) and Japanese Patent Application under PCTlaid-open under kohyo No. 10-505092 (WO96/7646).

WO97/25316 discloses the following compound A and the like, wherein theuse thereof is for a treatment of viral infection. The target virus is aDNA virus such as hepatitis B virus and the like. However, thispublication does not include the compound disclosed in the presentspecification or a description regarding or suggestive of HCV.

Japanese Patent Application under PCT laid-open under kohyo No.10-505092 discloses the following compound B and the like, wherein theuse thereof is for a treatment of viral infection. The target virus is aDNA virus such as herpesvirus and hepatitis B virus. However, thispublication does not include the compound disclosed in the presentspecification or a description regarding or suggestive of HCV.

The benzimidazole derivatives having an antiviral activity have beendisclosed in JP-A-3-31264, U.S. Pat. No. 3,644,382 and U.S. Pat. No.3,778,504. In addition, WO98/37072 discloses, as a production inhibitorof tumor necrosis factor (TNF) and cyclic AMP, a benzimidazolederivative for the use as an anti-human immunodeficiency virus (HIV)agent and an anti-inflammation agent. WO98/05327 discloses, as a reversetranscriptase inhibitor, a benzimidazole derivative for the use as ananti-HIV agent. J. Med. Chem. (13(4), 697-704, 1970) discloses, as aneuraminidase inhibitor, a benzimidazole derivative for the use as ananti-influenza virus agent.

However, none of these publications includes the compound of the presentinvention or a description regarding or suggestive of an anti-HCVeffect.

Known benzimidazole derivatives having a pharmaceutical use other thanas an antiviral agent are disclosed in JP-A-8-501318 (U.S. Pat. No.5,814,651) and JP-A-8-134073 (U.S. Pat. No. 5,563,143). Thesepublications disclose the following compound C and the like as acatechol diether compound, and the use thereof as an anti-inflammationagent. However, neither of the publications includes the compound of thepresent invention, and as the action mechanism, the former disclosesphosphodiesterase IV and the latter discloses TNF. These publications donot include a description regarding or suggestive of an anti-HCV effect.

Japanese Patent Application under PCT laid-open under kohyo No.2000-159749 (EP882718) discloses the following compound G and the like,and the use thereof for the treatment of bronchitis, glomerulonephritisand the like. However, this publication does not include the compound ofthe present invention, but discloses only a phosphodiesterase IVinhibitory and hypoglycemic action. This publication does not include adescription regarding or suggestive of an anti-HCV effect.

U.S. Pat. No. 6,211,177 discloses the following compound H and the likewith their use as antitumor agents. However, this publication does notencompass the compound of the present invention, and does not discloseor suggest an anti-HCV effect.

WO98/50029, WO98/50030 and WO98/50031 disclose benzimidazole derivativesas an antitumor agent having a protein isoprenyl transferase action.While this publication discloses a wide scope of the claims, at least itdoes not include a compound analogous to the compound of the presentinvention or a description regarding or suggestive of an anti-HCVeffect.

JP-A-8-109169 (EP694535) discloses the application of a tachykininreceptor antagonist to treat an inflammatory disease, and WO96/35713discloses the application thereof as a growth hormone release promoterto treat a growth hormone-related disease such as osteoporosis and thelike. However, none of these publications includes a descriptionregarding or suggestive of an anti-HCV effect.

WO2001/21634 discloses the following compound I in a chemical library.However, this publication does not encompass the compound of the presentinvention. While it discloses an antimicrobial activity of certaincompounds, this publication does not teach or suggest an anti-HCVeffect.

JP-A-53-14735 discloses a benzimidazole derivative as a brightenerbesides its pharmaceutical use, but this publication does not includethe compound of the present invention.

SUMMARY OF THE INVENTION

Based on the findings from the preceding studies, it has been elucidatedthat a pharmaceutical agent having an anti-HCV activity is effective forthe prophylaxis and treatment of hepatitis C, and particularly ananti-HCV agent having an inhibitory activity on RNA-dependent RNApolymerase of HCV can be a prophylactic and therapeutic agent effectiveagainst hepatitis C and a prophylactic and therapeutic agent for thedisease caused by hepatitis C.

Accordingly, the present invention provides a pharmaceutical agenthaving an anti-HCV activity, particularly a pharmaceutical agent havingan RNA-dependent RNA polymerase inhibitory activity.

The present inventors have made an in-depth study of compounds having ananti-HCV activity, particularly RNA-dependent RNA polymerase inhibitoryactivity, and completed the present invention.

Thus, the present invention provides the following (1) to (88).

-   (1) A therapeutic agent for hepatitis C, which comprises a fused    ring compound of the following formula [I] or a pharmaceutically    acceptable salt thereof as an active ingredient:    wherein-   a broken line is a single bond or a double bond,-   G¹ is C(—R¹) or a nitrogen atom,-   G² is C(—R²) or a nitrogen atom,-   G³ is C(—R³) or a nitrogen atom,-   G⁴ is C(—R⁴) or a nitrogen atom,-   G⁵, G⁶, G⁸ and G⁹ are each independently a carbon atom or a nitrogen    atom,-   G⁷ is C(—R⁷), an oxygen atom, a sulfur atom, or a nitrogen atom    optionally substituted by R⁸,    -   wherein R¹, R², R³ and R⁴ are each independently,    -   (1) hydrogen atom,    -   (2) C₁₋₆ alkanoyl,    -   (3) carboxyl,    -   (4) cyano,    -   (5) nitro,    -   (6) C₁₋₆ alkyl optionally substituted by 1 to 3 substituent(s)        selected from the following group A,        -   group A; halogen atom, hydroxyl group, carboxyl, amino, C₁₋₆            alkoxy, C₁₋₆ alkoxy C₁₋₆ alkoxy, C₁₋₆ alkoxycarbonyl and            C₁₋₆ alkylamino,    -   (7) —COOR^(a1)        -   wherein R^(a1) is optionally substituted C₁₋₆ alkyl (as            defined above), C₆₋₁₄ aryl C₁₋₆ alkyl optionally substituted            by 1 to 5 substituent(s) selected from the following group B            or glucuronic acid residue,        -   group B; halogen atom, cyano, nitro, C₁₋₆ alkyl, halogenated            C₁₋₆ alkyl, C₁₋₆ alkanoyl, —(CH₂)_(r)—COOR^(b1),            —(CH₂)_(r)—CONR^(b1)R^(b2), —(CH₂)_(r)—NR^(b1)R^(b2),            —(CH₂)_(r)—NR^(b1)—COR^(b2), —(CH₂)_(r)—NHSO₂R^(b1),            —(CH₂)_(r)—OR^(b1), —(CH₂)_(r)—SR^(b1), —(CH₂)_(r)—SO₂R^(b1)            and —(CH₂)_(r)—SO₂NR^(b1)R^(b2),            -   wherein R^(b1) and R^(b2) are each independently                hydrogen atom or C₁₋₆ alkyl and r is 0 or an integer of                1 to 6,    -   (8) —CONR^(a2)R^(a3)        -   wherein R^(a2) and R^(a3) are each independently hydrogen            atom, C₁₋₆ alkoxy or optionally substituted C₁₋₆ alkyl (as            defined above),    -   (9) —C(═NR^(a4))NH₂        -   wherein R^(a4) is hydrogen atom or hydroxyl group,    -   (10) —NHR^(a5)        -   wherein R^(a5) is hydrogen atom, C₁₋₆ alkanoyl or C₁₋₆            alkylsulfonyl,    -   (11) —OR⁸⁶        -   wherein R^(a6) is hydrogen atom or optionally substituted            C₁₋₆ alkyl (as defined above),    -   (12) —SO₂R^(a7)        -   wherein R^(a7) is hydroxyl group, amino, C₁₋₆ alkyl or C₁₋₆            alkylamino,    -   (13) —P(═O)(OR^(a31))₂        -   wherein R^(a31) is hydrogen atom, optionally substituted            C₁₋₆ alkyl (as defined above) or C₆₋₁₄ aryl C₁₋₆ alkyl            optionally substituted by 1 to 5 substituent(s) selected            from the above group B    -   or    -   (14) heterocyclic group having 1 to 4 heteroatom(s) selected        from an oxygen atom, a nitrogen atom and a sulfur atom, and    -   R⁷ and R⁸ are each hydrogen atom or optionally substituted C₁₋₆        alkyl (as defined above),-   ring Cy is    -   (1) C₃₋₈ cycloalkyl optionally substituted by 1 to 5        substituent(s) selected from the following group C,        -   group C; hydroxyl group, halogen atom, C₁₋₆ alkyl and C₁₋₆            alkoxy,    -   (2) C₃₋₈ cycloalkenyl optionally substituted by 1 to 5        substituent(s) selected from the above group C, or        -   wherein u and v are each independently an integer of 1 to 3,-   ring A is    -   (1) C₆₋₁₄ aryl,    -   (2) C₃₋₈ cycloalkyl,    -   (3) C₃₋₈ cycloalkenyl or    -   (4) heterocyclic group having 1 to 4 heteroatom(s) selected from        an oxygen atom, a nitrogen atom and a sulfur atom,-   R⁵ and R⁶ are each independently    -   (1) hydrogen atom,    -   (2) halogen atom,    -   (3) optionally substituted C₁₋₆ alkyl (as defined above) or    -   (4) —OR^(a8)        -   wherein R^(a8) is hydrogen atom, C₁₋₆ alkyl or C₆₋₁₄ aryl            C₁₋₆ alkyl, and-   X is    -   (1) hydrogen atom,    -   (2) halogen atom,    -   (3) cyano,    -   (4) nitro,    -   (5) amino, C₁₋₆ alkanoylamino,    -   (6) C₁₋₆ alkylsulfonyl,    -   (7) optionally substituted C₁₋₆ alkyl (as defined above),    -   (8) C₂₋₆ alkenyl optionally substituted by 1 to 3 substituent(s)        selected from the above group A,    -   (9) —COOR^(a9)        -   wherein R^(a9) is hydrogen atom or C₁₋₆ alkyl,    -   (10) —CONH— (CH₂)_(l)—R^(a10)        -   wherein R^(a10) is optionally substituted C₁₋₆ alkyl (as            defined above), C₁₋₆ alkoxycarbonyl or C₁₋₆ alkanoylamino            and l is 0 or an integer of 1 to 6,    -   (11) —OR^(a11)        -   wherein R^(a11) is hydrogen atom or optionally substituted            C₁₋₆ alkyl (as defined above)    -   or        -   wherein        -   ring B is        -   (1′) C₆₋₁₄ aryl,        -   (2′) C₃₋₈ cycloalkyl or        -   (3′) heterocyclic group (as defined above),        -   each Z is independently        -   (1′) a group selected from the following group D,        -   (2′) C₆₋₁₄ aryl optionally substituted by 1 to 5            substituent(s) selected from the following group D,        -   (3′) C₃₋₈ cycloalkyl optionally substituted by 1 to 5            substituent(s) selected from the following group D,        -   (4′) C₆₋₁₄ aryl C₁₋₆ alkyl optionally substituted by 1 to 5            substituent(s) selected from the following group D,        -   (5′) heterocyclic group optionally substituted by 1 to 5            substituent(s) selected from the following group D,        -   wherein the heterocyclic group has 1 to 4 hetero-atom(s)            selected from an oxygen atom, a nitrogen atom and a sulfur            atom, or        -   (6′) heterocycle C₁₋₆ alkyl optionally substituted by 1 to 5            substituent(s) selected from the following group D,        -   wherein the heterocycle C₁₋₆ alkyl is C₁₋₆ alkyl substituted            by heterocyclic group optionally substituted by 1 to 5            substituent(s) selected from the group D, as defined above,            -   group D:            -   (a) hydrogen atom,            -   (b) halogen atom,            -   (c) cyano,            -   (d) nitro,            -   (e) optionally substituted C₁₋₆ alkyl (as defined                above),            -   (f) —(CH₂)_(t)—COR^(a18),            -   (hereinafter each t means independently 0 or an integer                of 1 to 6),                -   wherein R^(a18) is                -   (1″) optionally substituted C₁₋₆ alkyl (as defined                    above),                -   (2″) C₆₋₁₄ aryl optionally substituted by 1 to 5                    substituent(s) selected from the above group B or                -   (3″) heterocyclic group optionally substituted by 1                    to 5 substituent(s) selected from the above group B                -    wherein the heterocyclic group has 1 to 4                    heteroatom(s) selected from an oxygen atom, a                    nitrogen atom and a sulfur atom,            -   (g) —(CH₂)_(t)—COOR^(a19)                -   wherein R^(a19) is hydrogen atom, optionally                    substituted C₁₋₆ alkyl (as defined above) or C₆₋₁₄                    aryl C₁₋₆ alkyl optionally substituted by 1 to 5                    substituent(s) selected from the above group B,            -   (h) —(CH₂)_(t)—CONR^(a27)R^(a28)                -   wherein R^(a27) and R^(a28) are each independently,                -   (1″) hydrogen atom,                -   (2″) optionally substituted C₁₋₆ alkyl (as defined                    above),                -   (3″) C₆₋₁₄ aryl optionally substituted by 1 to 5                    substituent(s) selected from the above group B,                -   (4″) C₆₋₁₄ aryl C₁₋₆ alkyl optionally substituted by                    1 to 5 substituent(s) selected from the above group                    B,                -   (5″) heterocyclic group optionally substituted by 1                    to 5 substituent(s) selected from the above group B,                -   (6″) heterocycle C₁₋₆ alkyl optionally substituted                    by 1 to 5 substituent(s) selected from the above                    group B,            -   wherein the heterocycle C₁₋₆ alkyl is C₁₋₆ alkyl                substituted by heterocyclic group optionally substituted                by 1 to 5 substituent(s) selected from the above group                B, as defined above,                -   (7″) C₃₋₈ cycloalkyl optionally substituted by 1 to                    5 substituent(s) selected from the above group B,                -   (8″) C₃₋₈ cycloalkyl C₁₋₆ alkyl optionally                    substituted by 1 to 5 substituent(s) selected from                    the above group B,                -   (9″) hydroxyl group or                -   (10″) C₁₋₆ alkoxy,            -   (i) —(CH₂)_(t)—C(═NR^(a33))NH₂                -   wherein R^(a33) is hydrogen atom, C₁₋₆ alkyl,                    hydroxyl group or C₁₋₆ alkoxy,            -   (j) —(CH₂)—OR^(a20)                -   wherein R^(a20) is                -   (1″) hydrogen atom,                -   (2″) optionally substituted C₁₋₆ alkyl (as defined                    above),                -   (3″) optionally substituted C₂₋₆ alkenyl (as defined                    above),                -   (4″) C₂₋₆ alkynyl optionally substituted by 1 to 3                    substituent(s) selected from the above group A,                -   (5″) C₆₋₁₄ aryl optionally substituted by 1 to 5                    substituent(s) selected from the above group B,                -   (6″) C₆₋₁₄ aryl C₁₋₆ alkyl optionally substituted by                    1 to 5 substituent(s) selected from the above group                    B,                -   (7″) heterocyclic group optionally substituted by 1                    to 5 substituent(s) selected from the above group B,                -   (8″) heterocycle C₁₋₆ alkyl optionally substituted                    by 1 to 5 substituent(s) selected from the above                    group B,                -   (9″) C₃₋₈ cycloalkyl optionally substituted by 1 to                    5 substituent(s) selected from the above group B, or                -   (10″) C₃₋₈ cycloalkyl C₁₋₆ alkyl optionally                    substituted by 1 to 5 substituent(s) selected from                    the above group B,            -   (k) —(CH₂)_(t)—O— (CH₂)_(p)—COR^(a21)                -   wherein R^(a21) is amino, C₁₋₆ alkylamino or                    heterocyclic group optionally substituted by 1 to 5                    substituent(s) selected from the above group B, and                    p is 0 or an integer of 1 to 6,            -   (1) —(CH₂)_(t)—NR^(a22)R^(a23)                -   wherein R^(a22) and R^(a23) are each independently                -   (1″) hydrogen atom,                -   (2″) optionally substituted C₁₋₆ alkyl (as defined                    above),                -   (3″) C₆₋₁₄ aryl optionally substituted by 1 to 5                    substituent(s) selected from the above group B,                -   (4″) C₆₋₁₄ aryl C₁₋₆ alkyl optionally substituted by                    1 to 5 substituent(s) selected from the above group                    B,                -   (5″) heterocycle C₁₋₆ alkyl optionally substituted                    by 1 to 5 substituent(s) selected from the above                    group B or                -   (6″) heterocyclic group optionally substituted by 1                    to 5 substituent(s) selected from the above group B,            -   (m) —(CH₂)_(t)—NR^(a29) CO—R^(a24)                -   wherein R^(a29) is hydrogen atom, C₁₋₆ alkyl or C₁₋₆                    alkanoyl, and R^(a24) is                -   (1″) amino,                -   (2″) C₁₋₆ alkylamino,                -   (3″) optionally substituted C₁₋₆ alkyl (as defined                    above),                -   (4″) C₆₋₁₄ aryl optionally substituted by 1 to 5                    substituent(s) selected from the above group B,                -   (5″) heterocyclic group optionally substituted by 1                    to 5 substituent(s) selected from the above group B                    or                -   (6″) heterocycle C₁₋₆ alkyl optionally substituted                    by 1 to 5 substituent(s) selected from the above                    group B,            -   (n) —(CH₂)_(t)—NR^(a29)SO₂—R^(a25)                -   wherein R^(a29) is as defined above, and                -   R^(a25) is hydrogen atom, optionally substituted                    C₁₋₆ alkyl (as defined above), C₆₋₁₄ aryl optionally                    substituted by 1 to 5 substituent(s) selected from                    the above group B or heterocyclic group optionally                    substituted by 1 to 5 substituent(s) selected from                    the above group B,            -   (o) —(CH₂)_(t)—S(O)_(q)—R^(a25)                -   wherein R^(a25) is as defined above, and q is 0, 1                    or 2,            -   (p) —(CH₂)_(t)—SO₂—NHR^(a26)                -   wherein R^(a26) is hydrogen atom, optionally                    substituted C₁₋₆ alkyl (as defined above), C₆₋₁₄                    aryl optionally substituted by 1 to 5 substituent(s)                    selected from the above group B or heterocyclic                    group optionally substituted by 1 to 5                    substituent(s) selected from the above group B,            -   and            -   (q) heterocyclic group having 1 to 4 heteroatom(s)                selected from an oxygen atom, a nitrogen atom and a                sulfur atom, and        -   w is an integer of 1 to 3, and        -   Y is            -   (1′) a single bond,            -   (2′) C₁₋₆ alkylene,            -   (3′) C₂₋₆ alkenylene,            -   (4′) —(CH₂)_(m)—O—(CH₂)_(n)—,                -   (hereinafter m and n are each independently 0 or an                    integer of 1 to 6),            -   (5′) —CO—,            -   (6′) —CO₂— (CH₂)_(n)—,            -   (7′) —CONH— (CH₂)_(n)—NH—,            -   (8′) —NHCO₂—,            -   (9′) —NHCONH—,            -   (10′) —O—(CH₂)_(n)—CO—,            -   (11′) —O—(CH₂)_(n)—O—,            -   (12′) —SO₂—,            -   (13′) —(CH₂)_(m)—NR^(a12)—(CH₂)_(n)—                -   wherein R^(a12) is                -   (1″) hydrogen atom,                -   (2″) optionally substituted C₁₋₆ alkyl (as defined                    above),                -   (3″) C₆₋₁₄ aryl C₁₋₆ alkyl optionally substituted by                    1 to 5 substituent(s) selected from the above group                    B,                -   (4″) C₆₋₁₄ aryl optionally substituted by 1 to 5                    substituent(s) selected from the above group B,                -   (5″) COR^(b5)                -    wherein R^(b5) is hydrogen atom, optionally                    substituted C₁₋₆ alkyl (as defined above), C₆₋₁₄                    aryl optionally substituted by 1 to 5 substituent(s)                    selected from the above group B or C₆₋₁₄ aryl C₁₋₆                    alkyl optionally substituted by 1 to 5                    substituent(s) selected from the above group B,                -   (6″) —COOR^(b5) (R^(b5) is as defined above) or                -   (7″) —SO₂R^(b5) (R^(b5) is as defined above),            -   (14′) —NR^(a12)CO— (R^(a12) is as defined above),            -   (15′) —CONR^(a13)—(CH₂)_(n)—                -   wherein R^(a13) is hydrogen atom, optionally                    substituted C₁₋₆ alkyl (as defined above) or C₆₋₁₄                    aryl C₁₋₆ alkyl optionally substituted by 1 to 5                    substituent(s) selected from the above group B,            -   (16) —CONH—CHR^(a14)—                -   wherein R^(a14) is C₆₋₁₄ aryl optionally substituted                    by 1 to 5 substituent(s) selected from the above                    group B,            -   (17) O— (CH₂)_(m)—CR^(a15)R^(a16)—(CH₂)_(n)—                -   wherein R^(a15) and R^(a16) are each independently                -   (1″) hydrogen atom,                -   (2″) carboxyl,                -   (3″) C₁₋₆ alkyl,                -   (4″) —OR^(b6)                -   wherein R^(b6) is C₁₋₆ alkyl or C₆₋₁₄ aryl C₁₋₆                    alkyl,                -   or                -   (5″) —NHR^(b7)                -   wherein R^(b7) is hydrogen atom, C₁₋₆ alkyl, C₁₋₆                    alkanoyl or C₆₋₁₄ aryl C₁₋₆ alkyloxycarbonyl, or                    R^(a15) is optionally                -    wherein n′, ring B′, Z′ and w′ are the same as the                    above-mentioned n, ring B, Z and w, respectively,                    and may be the same as or different from the                    respective counterparts,            -   (18′) —(CH₂)_(n)—NR^(a12)—CHR^(a15)—(R^(a12) and R^(a15)                are each as defined above),            -   (19′) —NR^(a17)SO₂                -   wherein R^(a17) is hydrogen atom or C₁₋₆ alkyl,            -   (20′) —S(O)_(e)—(CH₂)_(m)—CR^(a15)R^(a16)—(CH₂)_(n)— (e                is 0, 1 or 2, R^(a15) and R^(a16) are each as defined                above),            -   or            -   (21) —(CH₂)_(m)—CR^(a15)R^(a16)—(CH₂)_(n)— (R^(a15) and                R^(a16) are each as defined above).-   (2) The therapeutic agent of (1) above, wherein 1 to 4 of the G¹,    G², G³, G⁴, G⁵, G⁶, G⁷, G⁸ and G⁹ is (are) a nitrogen atom.-   (3) The therapeutic agent of (2) above, wherein G² is C(—R²) and G⁶    is a carbon atom.-   (4) The therapeutic agent of (2) or (3) above, wherein G⁵ is a    nitrogen atom.-   (5) The therapeutic agent of (1) above, wherein, in formula [I], the    moiety    is a fused ring selected from-   (6) The therapeutic agent of (5) above, wherein, in formula [I], the    moiety    is a fused ring selected from-   (7) The therapeutic agent of (6) above, which comprises a fused ring    compound of the following formula [I-1]    wherein each symbol is as defined in (1),    or a pharmaceutically acceptable salt thereof as an active    ingredient.-   (8) The therapeutic agent of (6) above, which comprises a fused ring    compound of the following formula [I-2]    wherein each symbol is as defined in (1),    or a pharmaceutically acceptable salt thereof as an active    ingredient.-   (9) The therapeutic agent of (6) above, which comprises a fused ring    compound of the following formula [I-3]    wherein each symbol is as defined in (1),    or a pharmaceutically acceptable salt thereof as an active    ingredient.-   (10) The therapeutic agent of (6) above, which comprises a fused    ring compound of the following formula [I-4]    wherein each symbol is as defined in (1),    or a pharmaceutically acceptable salt thereof as an active    ingredient.-   (11) The therapeutic agent of any of (1) to (10) above, wherein at    least one of R¹, R², R³ and R⁴ is carboxyl, —COOR^(a1),    —CONR^(a2)R^(a3), —SO₂R^(a7) (wherein R^(a1), R^(a2), R^(a3) and    R^(a7) are as defined in (1)),-   (12) The therapeutic agent of (11) above, wherein at least one of    R¹, R², R³ and R⁴ is carboxyl, —COOR^(a1), —CONR^(a2)R^(a3) or    —SO₂R^(a7) wherein R^(a1), R^(a2), R^(a3) and R^(a7) are as defined    in (1).-   (13) The therapeutic agent of any of (1) to (10) above, wherein at    least one of R¹, R², R³ and R⁴ is —COOR^(a1) wherein R^(a1) is    glucuronic acid residue.-   (14) The therapeutic agent of any of (1) to (10) above, wherein at    least one of R¹, R², R³ and R⁴ is heterocyclic group having 1 to 4    heteroatom(s) selected from an oxygen atom, a nitrogen atom and a    sulfur atom.-   (15) The therapeutic agent of any of (1) to (14) above, wherein the    ring Cy is cyclopentyl, cyclohexyl, cycloheptyl,    tetrahydrothiopyranyl or piperidino.-   (16) The therapeutic agent of any of (1) to (14) above, wherein the    ring Cy is    wherein each symbol is as defined in (1).-   (17) The therapeutic agent of any of (1) to (16) above, wherein the    ring A is C₆₋₁₄ aryl.-   (18) The therapeutic agent of any of (1) to (17) above, wherein at    least one substituent optionally substituted by group A is a    substituent substituted by C₁₋₆ alkoxy C₁₋₆ alkoxy.-   (19) The therapeutic agent of any of (1) to (18) above, wherein the    Y is —(CH₂)_(m)—CR^(a15)R^(a16)—(CH₂)_(n)— wherein each symbol is as    defined in (1).-   (20) The therapeutic agent of any of (1) to (19) above, wherein at    least one group represented by Z is heterocycle C₁₋₆ alkyl    optionally substituted by 1 to 5 substituent(s) selected from the    group D.-   (21) The therapeutic agent of any of (1) to (19) above, wherein at    least one group represented by Z is a heterocyclic group optionally    substituted by 1 to 5 substituent(s) selected from the group D,    wherein said heterocyclic group is selected from the following    groups:    wherein E¹ is an oxygen atom, a sulfur atom or N(—R^(a35)), E² is an    oxygen atom, CH₂ or N(—R^(a35)), E³ is an oxygen atom or a sulfur    atom, wherein each R^(a35) is independently hydrogen atom or C₁₋₆    alkyl, f is an integer of 1 to 3, and h and h′ are the same or    different and each is an integer of 1 to 3.-   (22) The therapeutic agent of (21) above, wherein at least one group    represented by Z is heterocyclic group optionally substituted by 1    to 5 substituent(s) selected from the group D wherein said    heterocyclic group is selected from the following groups:    wherein each symbol is as defined in (21).-   (23) The therapeutic agent of any of (1) to (19) above, wherein at    least one group represented by group D is    —(CH₂)_(t)—CONR^(a27)R^(a28) wherein each symbol is as defined in    (1), and at least one of R^(a27) and R^(a28) is C₁₋₆ alkoxy.-   (24) The therapeutic agent of any of (1) to (19) above, wherein at    least one group represented by group D is —(CH₂)_(t)—C(═NR^(a33))NH₂    wherein each symbol is as defined in (1), and R^(a33) is hydroxyl    group or C₁₋₆ alkoxy.-   (25) The therapeutic agent of any of (1) to (19) above, wherein at    least one group represented by group D is    —(CH₂)_(t)—O—(CH₂)_(p)—COR^(a21), wherein each symbol is as defined    in (1), and R^(a21) is amino.-   (26) The therapeutic agent of any of (1) to (19) above, wherein at    least one group represented by group D is    —(CH₂)_(t)—NR^(a29)CO—R^(a24) wherein each symbol is as defined in    (1), and R^(a24) is amino or C₁₋₆ alkylamino.-   (27) The therapeutic agent of any of (1) to (19) above, wherein at    least one group represented by group D is —(CH₂)_(t)—NR^(a22)R^(a23)    wherein each symbol is as defined in (1), and at lease one of    R^(a22) and R^(a23) is heterocyclic group optionally substituted by    1 to 5 substituent(s) selected from the group B.-   (28) The therapeutic agent of any of (1) to (19) above, wherein at    least one group represented by group D is heterocyclic group having    1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen atom    and a sulfur atom.-   (29) A fused ring compound of the following formula [II]    wherein    the moiety    is a fused ring selected from    -   wherein R¹, R², R³ and R⁴ are each independently,    -   (1) hydrogen atom,    -   (2) C₁₋₆ alkanoyl,    -   (3) carboxyl,    -   (4) cyano,    -   (5) nitro,    -   (6) C₁₋₆ alkyl optionally substituted by 1 to 3 substituent(s)        selected from the following group A,        -   group A; halogen atom, hydroxyl group, carboxyl, amino, C₁₋₆            alkoxy, C₁₋₆ alkoxy C₁₋₆ alkoxy, C₁₋₆ alkoxycarbonyl and            C₁₋₆ alkylamino,    -   (7) —COOR^(a1)        -   wherein R^(a1) is optionally substituted C₁₋₆ alkyl (as            defined above), C₆₋₁₄ aryl C₁₋₆ alkyl optionally substituted            by 1 to 5 substituent(s) selected from the following group B            or glucuronic acid residue,        -   group B; halogen atom, cyano, nitro, C₁₋₆ alkyl, halogenated            C₁₋₆ alkyl, C₁₋₆ alkanoyl, —(CH₂)_(r)—COOR^(b1),            —(CH₂)_(r)—CONR^(b1)R^(b2), —(CH₂)_(r)—NR^(b1)R^(b2),            —(CH₂)_(r)—NR^(b1) COR^(b2), —(CH₂)_(r)—NHSO₂R^(b1),            —(CH₂)_(r)—OR^(b1), —(CH₂)_(r)—SR^(b1), —(CH₂)_(r)—SO₂R^(b1)            and —(CH₂)_(r)—SO₂NR^(b1)R^(b2)            -   wherein R^(b1) and R^(b2) are each independently                hydrogen atom or C₁₋₆ alkyl and r is 0 or an integer of                1 to 6,    -   (8) —CONR^(a2)R^(a3)        -   wherein R^(a2) and R^(a3) are each independently hydrogen            atom, C₁₋₆ alkoxy or optionally substituted C₁₋₆ alkyl (as            defined above),    -   (9) —C(═NR^(a4))NH₂        -   wherein R^(a4) is hydrogen atom or hydroxyl group,    -   (10) —NHR^(a5)        -   wherein R^(a5) is hydrogen atom, C₁₋₆ alkanoyl or C₁₋₆            alkylsulfonyl,    -   (11) —OR^(a6)        -   wherein R^(a6) is hydrogen atom or optionally substituted            C₁₋₆ alkyl (as defined above),    -   (12) —SO₂R^(a7)        -   wherein R^(a7) is hydroxyl group, amino, C₁₋₆ alkyl or C₁₋₆            alkylamino,    -   (13) —P(═O)(OR^(a31))₂        -   wherein R^(a31) is hydrogen atom, optionally substituted            C₁₋₆ alkyl (as defined above) or C₆₋₁₄ aryl C₁₋₆ alkyl            optionally substituted by 1 to 5 substituent(s) selected            from the above group B,    -   or    -   (14) heterocyclic group having 1 to 4 heteroatom(s) selected        from an oxygen atom, a nitrogen atom and a sulfur atom, and    -   R⁷ is hydrogen atom or optionally substitute C₁₋₆ alkyl (as        defined above),-   ring Cy′ is    -   (1) C₃₋₈ cycloalkyl optionally substituted by 1 to 5        substituent(s) selected from the following group C,        -   group C; hydroxyl group, halogen atom, C₁₋₆ alkyl and C₁₋₆            alkoxy, or            -   wherein u and v are each independently an integer of 1                to 3,-   ring A′ is a group selected from a group consisting of phenyl,    pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, cyclohexyl,    cyclohexenyl, furyl and thienyl,-   R^(5′) and R^(6′) are each independently    -   (1) hydrogen atom,    -   (2) halogen atom,    -   (3) optionally substituted C₁₋₆ alkyl (as defined above) or    -   (4) hydroxyl group-   ring B is    -   (1) C₆₋₁₄ aryl,    -   (2) C₃₋₈ cycloalkyl or    -   (3) heterocyclic group having 1 to 4 heteroatom(s) selected from        an oxygen atom, a nitrogen atom and a sulfur atom,-   each Z is independently    -   (1) a group selected from the following group D,    -   (2) C₆₋₁₄ aryl optionally substituted by 1 to 5 substituent(s)        selected from the following group D,    -   (3) C₃₋₈ cycloalkyl optionally substituted by 1 to 5        substituent(s) selected from the following group D,    -   (4) C₆₋₁₄ aryl C₁₋₆ alkyl optionally substituted by 1 to 5        substituent(s) selected from the following group D,    -   (5) heterocyclic group optionally substituted by 1 to 5        substituent(s) selected from the following group D wherein the        heterocyclic group has 1 to 4 heteroatom(s) selected from an        oxygen atom, a nitrogen atom and a sulfur atom, or    -   (6) heterocycle C₁₋₆ alkyl optionally substituted by 1 to 5        substituent(s) selected from the following group D wherein the        heterocycle C₁₋₆ alkyl is C₁₋₆ alkyl substituted by heterocyclic        group optionally substituted by 1 to 5 substituent(s) selected        from the group D, as defined above,    -    group D:        -   (a) hydrogen atom,        -   (b) halogen atom,        -   (c) cyano,        -   (d) nitro,        -   (e) optionally substituted C₁₋₆ alkyl (as defined above),        -   (f) —(CH₂)_(t)—COR^(a18),        -   (hereinafter each t means independently 0 or an integer of 1            to 6),            -   wherein R^(a18) is            -   (1′) optionally substituted C₁₋₆ alkyl (as defined                above),            -   (2′) C₆₋₁₄ aryl optionally substituted by 1 to 5                substituent(s) selected from the above group B or            -   (3′) heterocyclic group optionally substituted by 1 to 5                substituent(s) selected from the above group B                -   wherein the heterocyclic group has 1 to 4                    heteroatom(s) selected from an oxygen atom, a                    nitrogen atom and a sulfur atom,        -   (g) —(CH₂)_(t)—COOR^(a19)        -   wherein R^(a19) is hydrogen atom, optionally substituted            C₁₋₆ alkyl (as defined above) or C₆₋₁₄ aryl C₁₋₆ alkyl            optionally substituted by 1 to 5 substituent(s) selected            from the above group B,        -   (h) —(CH₂)_(t)—CONR^(a27)R^(a28)        -   wherein R^(a27) and R^(a28) are each independently,        -   (1′) hydrogen atom,        -   (2′) optionally substituted C₁₋₆ alkyl (as defined above),        -   (3′) C₆₋₁₄ aryl optionally substituted by 1 to 5            substituent(s) selected from the above group B,        -   (4′) C₆₋₁₄ aryl C₁₋₆ alkyl optionally substituted by 1 to 5            substituent(s) selected from the above group B,        -   (5′) heterocyclic group optionally substituted by 1 to 5            substituent(s) selected from the above group B,        -   (6′) heterocycle C₁₋₆ alkyl optionally substituted by 1 to 5            substituent(s) selected from the above group B,        -   wherein the heterocycle C₁₋₆ alkyl is C₁₋₆ alkyl substituted            by heterocyclic group optionally substituted by 1 to 5            substituent(s) selected from the above group B, as defined            above,        -   (7′) C₃₋₈ cycloalkyl optionally substituted by 1 to 5            substituent(s) selected from the above group B,        -   (8′) C₃₋₈ cycloalkyl C₁₋₆ alkyl optionally substituted by 1            to 5 substituent(s) selected from the above group B,        -   (9′) hydroxyl group or        -   (10′) C₁₋₆ alkoxy,        -   (i) —(CH₂)_(t)—C(═NR^(a33))NH₂        -   wherein R^(a33) is hydrogen atom, C₁₋₆ alkyl, hydroxyl group            or C₁₋₆ alkoxy,        -   (j) —(CH₂)_(t)—OR^(a20)        -   wherein R^(a20) is        -   (1′) hydrogen atom,        -   (2′) optionally substituted C₁₋₆ alkyl (as defined above),        -   (3′) optionally substituted C₂₋₆ alkenyl (as defined above),        -   (4′) C₂₋₆ alkynyl optionally substituted by 1 to 3            substituent(s) selected from the above group A,        -   (5′) C₆₋₁₄ aryl optionally substituted by 1 to 5            substituent(s) selected from the above group B,        -   (6′) C₆₋₁₄ aryl C₁₋₆ alkyl optionally substituted by 1 to 5            substituent(s) selected from the above group B,        -   (7′) heterocyclic group optionally substituted by 1 to 5            substituent(s) selected from the above group B,        -   (8′) heterocycle C₁₋₆ alkyl optionally substituted by 1 to 5            substituent(s) selected from the above group B,        -   (9′) C₃₋₈ cycloalkyl optionally substituted by 1 to 5            substituent(s) selected from the above group B, or        -   (10′) C₃₋₈ cycloalkyl C₁₋₆ alkyl optionally substituted by 1            to 5 substituent(s) selected from the above group B,        -   (k) —(CH₂)_(t)—O— (CH₂)_(p)—COR^(a21)        -   wherein R^(a21) is amino, C₁₋₆ alkylamino or heterocyclic            group optionally substituted by 1 to 5 substituent(s)            selected from the above group B,        -   and p is 0 or an integer of 1 to 6,        -   (l) —(CH₂)_(t)—NR^(a22)R^(a23)        -   wherein R^(a22) and R^(a23) are each independently        -   (1′) hydrogen atom,        -   (2′) optionally substituted C₁₋₆ alkyl (as defined above),        -   (3′) C₆₋₁₄ aryl optionally substituted by 1 to 5            substituent(s) selected from the above group B,        -   (4′) C₆₋₁₄ aryl C₁₋₆ alkyl optionally substituted by 1 to 5            substituent(s) selected from the above group B,        -   (5′) heterocycle C₁₋₆ alkyl optionally substituted by 1 to 5            substituent(s) selected from the above group B or        -   (6′) heterocyclic group optionally substituted by 1 to 5            substituent(s) selected from the above group B,        -   (m) —(CH₂)_(t)—NR^(a29)CO—R^(a24)        -   wherein R^(a29) is hydrogen atom, C₁₋₆ alkyl or C₁₋₆            alkanoyl, and        -   R^(a24) is        -   (1′) amino,        -   (2′) C₁₋₆ alkylamino,        -   (3′) optionally substituted C₁₋₆ alkyl (as defined above),        -   (4′) C₆₋₁₄ aryl optionally substituted by 1 to 5            substituent(s) selected from the above group B,        -   (5′) heterocyclic group optionally substituted by 1 to 5            substituent(s) selected from the above group B, or        -   (6′) heterocycle C₁₋₆ alkyl optionally substituted by 1 to 5            substituent(s) selected from the above group B,        -   (n) —(CH₂)_(t)—NR^(a29)SO₂—R^(a25)        -   wherein R^(a29) is as defined above, and        -   R^(a25) is hydrogen atom, optionally substituted C₁₋₆ alkyl            (as defined above), C₆₋₁₄ aryl optionally substituted by 1            to 5 substituent(s) selected from the above group B or            heterocyclic group optionally substituted by 1 to 5            substituent(s) selected from the above group B,        -   (o) —(CH₂)_(t)—S(O)_(q)—R^(a25)        -   wherein R^(a25) is as defined above, and q is 0, 1 or 2,        -   (p) —(CH₂)_(t)—SO₂—NHR^(a26)        -   wherein R^(a26) is hydrogen atom, optionally substituted            C₁₋₆ alkyl (as defined above), C₆₋₁₄ aryl optionally            substituted by 1 to 5 substituent(s) selected from the above            group B or heterocyclic group optionally substituted by 1 to            5 substituent(s) selected from the above group B,        -   and        -   (q) heterocyclic group having 1 to 4 heteroatom(s) selected            from an oxygen atom, a nitrogen atom and a sulfur atom,-   w is an integer of 1 to 3, and-   Y is    -   (1) a single bond,    -   (2) C₁₋₆ alkylene,    -   (3) C₂₋₆ alkenylene,    -   (4) —(CH₂)_(m)—O— (CH₂)_(n)—,        -   (hereinafter m and n are each independently 0 or an integer            of 1 to 6),    -   (5) —CO—,    -   (6) —CO₂— (CH₂)_(n)—,    -   (7) —CONH— (CH₂) n-NH—,    -   (8) —NHCO₂—,    -   (9) —NHCONH—,    -   (10) —O—(CH₂)_(n)—CO—,    -   (11) —O— (CH₂)—O—,    -   (12) —SO₂—,    -   (13) —(CH₂)_(m)—NR^(a12)—(CH₂)_(n)—        -   wherein R^(a12) is        -   (1′) hydrogen atom,        -   (2′) optionally substituted C₁₋₆ alkyl (as defined above),        -   (3′) C₆₋₁₄ aryl C₁₋₆ alkyl optionally substituted by 1 to 5            substituent(s) selected from the above group B,        -   (4′) C₆₋₁₄ aryl optionally substituted by 1 to 5            substituent(s) selected from the above group B,        -   (5′) —COR^(b5)        -   wherein R^(b5) is hydrogen atom, optionally substituted C₁₋₆            alkyl (as defined above), C₆₋₁₄ aryl optionally substituted            by 1 to 5 substituent(s) selected from the above group B or            C₆₋₁₄ aryl C₁₋₆ alkyl optionally substituted by 1 to 5            substituent(s) selected from the above group B,        -   (6′) —COOR⁵ (R^(b5) is as defined above) or        -   (7′) —SO₂R^(b5) (R^(b5) is as defined above),    -   (14) —NR^(a12)CO— (R^(a12) is as defined above),    -   (15) —CONR^(a13)—(CH₂) n        -   wherein R^(a13) is hydrogen atom, optionally substituted            C₁₋₆ alkyl (as defined above) or C₆₋₁₄ aryl C₁₋₆ alkyl            optionally substituted by 1 to 5 substituent(s) selected            from the above group B,    -   (16) —CONH—CHR^(a14)—        -   wherein R^(a14) is C₆₋₁₄ aryl optionally substituted by 1 to            5 substituent(s) selected from the above group B,    -   (17) —O— (CH₂)_(m)—CR^(a15)R^(a16)—(CH₂)_(n)—        -   wherein R^(a15) and R^(a16) are each independently        -   (1′) hydrogen atom,        -   (2′) carboxyl,        -   (3′) C₁₋₆ alkyl,        -   (4′) —OR^(b6)        -   wherein R^(b6) is C₁₋₆ alkyl or C₆₋₁₄ aryl C₁₋₆ alkyl,        -   or        -   (5′) —NHR^(b7)        -   wherein R^(b7) is hydrogen atom, C₁₋₆ alkyl, C₁₋₆ alkanoyl            or C₆₋₁₄ aryl C₁₋₆ alkyloxycarbonyl, or R^(a15) is            optionally        -   wherein n′, ring B′, Z′ and w′ are the same as the            above-mentioned n, ring B, Z and w, respectively, and may be            the same as or different from the respective counterparts,    -   (18) —(CH₂)—NR^(a12)—CHR^(a15)—(R^(a12) and R^(a15) are each as        defined above),    -   (19) —NR^(a17)SO₂—        -   wherein R^(a17) is hydrogen atom or C₁₋₆ alkyl,    -   (20) —S(O)_(e)—(CH₂)_(m)—CR^(a15)R^(a16)—(CH₂)_(n)— (e is 0, 1        or 2, R^(a15) and R^(a16) are each as defined above),    -   or    -   (21) —(CH₂)_(m)—CR^(a15)R^(a16)—(CH₂)_(n)— (R^(a15) and R^(a16)        are each as defined above),        or a pharmaceutically acceptable salt thereof.-   (30) The fused ring compound of (29) above, which is represented by    the following formula [II-1]    wherein each symbol is as defined in (29),    or a pharmaceutically acceptable salt thereof.-   (31) The fused ring compound of (29) above, which is represented by    the following formula [II-2]    wherein each symbol is as defined in (29),    or a pharmaceutically acceptable salt thereof.    -   (32) The fused ring compound of (29) above, which is represented        by the following formula [II-3]        wherein each symbol is as defined in (29),        or a pharmaceutically acceptable salt thereof.-   (33) The fused ring compound of (29) above, which is represented by    the following formula [II-4]    wherein each symbol is as defined in (29),    or a pharmaceutically acceptable salt thereof.-   (34) The fused ring compound of any of (29) to (33) above, wherein    at least one of R¹, R², R³ and R⁴ is carboxyl, —COOR^(a1),    —CONR^(a2)R^(a3)—SO₂R^(a7) (wherein R^(a1), R^(a2), R^(a3) and    R^(a7) are as defined in (29)),    or a pharmaceutically acceptable salt thereof.-   (35) The fused ring compound of (34) above, wherein at least one of    R¹, R², R³ and R⁴ is carboxyl, —COOR^(a1) or —SO₂R^(a7) wherein    R^(a1) and R^(a7) are as defined in (29), or a pharmaceutically    acceptable salt thereof.-   (36) The fused ring compound of (35) above, wherein at least one of    R¹, R², R³ and R⁴ is carboxyl or —COOR^(a1) wherein R^(a1) is as    defined in (29), or a pharmaceutically acceptable salt thereof.-   (37) The fused ring compound of (36) above, wherein R² is carboxyl    and R¹, R³ and R⁴ are hydrogen atoms, or a pharmaceutically    acceptable salt thereof.-   (38) The fused ring compound of any of (29) to (33) above, wherein    at least one of R¹, R², R³ and R⁴ is —COOR^(a1) wherein R^(a1) is    glucuronic acid residue, or a pharmaceutically acceptable salt    thereof.-   (39) The fused ring compound of any of (29) to (33) above, wherein    at least one of R¹, R², R³ and R⁴ is heterocyclic group having 1 to    4 heteroatom(s) selected from an oxygen atom, a nitrogen atom and a    sulfur atom, or a pharmaceutically acceptable salt thereof.-   (40) The fused ring compound of any of (29) to (33) above, wherein    the ring Cy′ is cyclopentyl, cyclohexyl, cycloheptyl or    tetrahydrothiopyranyl, or a pharmaceutically acceptable salt    thereof.-   (41) The fused ring compound of (40) above, wherein the ring Cy′ is    cyclopentyl, cyclohexyl or cycloheptyl, or a pharmaceutically    acceptable salt thereof.-   (42) The fused ring compound of any of (29) to (39) above, wherein    the ring Cy′ is    wherein each symbol is as defined in (29), or a pharmaceutically    acceptable salt thereof.-   (43) The fused ring compound of any of (29) to (42) above, wherein    the ring A′ is phenyl, pyridyl, pyrazinyl, pyrimidinyl or    pyridazinyl, or a pharmaceutically acceptable salt thereof.-   (44) The fused ring compound of (43) above, wherein the ring A′ is    phenyl or pyridyl, or a pharmaceutically acceptable salt thereof.-   (45) The fused ring compound of (44) above, wherein the ring A′ is    phenyl, or a pharmaceutically acceptable salt thereof.-   (46) The fused ring compound of any of (29) to (45) above, wherein    at least one substituent optionaly substituted by group A is a    substituent substituted by C₁₋₆ alkoxy C₁₋₆ alkoxy, or a    pharmaceutically acceptable salt thereof.-   (47) The fused ring compound of any of (29) to (46) above, wherein    the Y is —(CH₂)_(m)—O—(CH₂)_(n)—, —NHCO₂—, —CONH—CHR^(a14)—,    —(CH₂)_(m)—NR^(a12)—(CH₂)_(n)—, —CONR^(a13)—(CH₂)_(n)—, —O—    (CH₂)_(m)—CR^(a15)R^(a16)—(CH₂)_(n)— or    —(CH₂)_(n)—NR^(a12)—CHR^(a15)— (wherein each symbol is as defined in    (29)),    or a pharmaceutically acceptable salt thereof.-   (48) The fused ring compound of (47) above, wherein the Y is    —(CH₂)_(m)—O—(CH₂)_(n)— or —O—(CH₂)_(m)—CR^(a15)R^(a16)—(CH₂)_(n)—    (wherein each symbol is as defined in (29)), or a pharmaceutically    acceptable salt thereof.-   (49) The fused ring compound of (48) above, wherein the Y is    —(CH₂)_(m)—O—(CH₂)_(n)— wherein each symbol is as defined in (29),    or a pharmaceutically acceptable salt thereof.-   (50) The fused ring compound of any of (29) to (46) above, wherein    the Y is —(CH₂)_(m)—CR^(a15)R^(a16)—(CH₂)_(n)— (wherein each symbol    is as defined in (29)), or a pharmaceutically acceptable salt    thereof.-   (51) The fused ring compound of any of (29) to (50) above, wherein    the R² is carboxyl, R¹, R³ and R⁴ are hydrogen atoms, the ring Cy′    is cyclopentyl, cyclohexyl or cycloheptyl, and the ring A′ is    phenyl, or a pharmaceutically acceptable salt thereof.-   (52) The fused ring compound of any of (29) to (51) above, wherein    at least one group represented by Z is heterocycle C₁₋₆ alkyl    optionally substituted by 1 to 5 substituent(s) selected from the    group D, or a pharmaceutically acceptable salt thereof.-   (53) The fused ring compound of any of (29) to (51) above, wherein    at least one group represented by Z is heterocyclic group optionally    substituted by 1 to 5 substituent(s) selected from the group D,    wherein said heterocyclic group is selected from the following    groups:    wherein E¹ is an oxygen atom, a sulfur atom or N(—R^(a35)), E² is an    oxygen atom, CH₂ or N(—R^(a35)), E³ is an oxygen atom or a sulfur    atom, wherein each R^(a35) is independently hydrogen atom or C₁₋₆    alkyl, f is an integer of 1 to 3, and h and h′ are the same or    different and each is an integer of 1 to 3, or a pharmaceutically    acceptable salt thereof.-   (54) The fused ring compound of (53) above, wherein at least one    group represented by Z is heterocyclic group optionally substituted    by 1 to 5 substituent(s) selected from the group D, wherein said    heterocyclic group is selected from the following groups:-   wherein each symbol is as defined in (53), or a pharmaceutically    acceptable salt thereof.-   (55) The fused ring compound of any of (29) to (51) above, wherein    at least one group represented by group D is    —(CH₂)_(t)—CONR^(a27)R^(a28) wherein each symbol is as defined in    (29), and at least one of R^(a27) and R^(a28) is C₁₋₆ alkoxy, or a    pharmaceutically acceptable salt thereof.-   (56) The fused ring compound of any of (29) to (51) above, wherein    at least one group represented by group D is    —(CH₂)_(t)—C(═NR^(a33))NH₂ wherein each symbol is as defined in    (29), and R^(a33) is hydroxyl group or C₁₋₆ alkoxy, or a    pharmaceutically acceptable salt thereof.-   (57) The fused ring compound of any of (29) to (51) above, wherein    at least one group represented by group D is    —(CH₂)_(t)—O—(CH₂)_(p)—COR^(a21) wherein each symbol is as defined    in (29), and R^(a21) is amino, or a pharmaceutically acceptable salt    thereof.-   (58) The fused ring compound of any of (29) to (51) above, wherein    at least one group represented by group D is    —(CH₂)_(t)—NR^(a29)CO—R^(a24) wherein each symbol is as defined in    (29), and R^(a24) is amino or C₁₋₆ alkylamino, or a pharmaceutically    acceptable salt thereof.-   (59) The fused ring compound of any of (29) to (51) above, wherein    at least one group represented by group D is    —(CH₂)_(t)—NR^(a22)R^(a23) wherein each symbol is as defined in    (29), and at least one of R^(a22) and R^(a23) is heterocyclic group    optionally substituted by 1 to 5 substituent(s) selected from the    group B, or a pharmaceutically acceptable salt thereof.-   (60) The fused ring compound of any of (29) to (51) above, wherein    at least one group represented by group D is heterocyclic group    having 1 to 4 heteroatom(s) selected from an oxygen atom, a nitrogen    atom and a sulfur atom, or a pharmaceutically acceptable salt    thereof.-   (61) The fused ring compound of the formula [I] or a    pharmaceutically acceptable salt thereof, which is selected from the    group consisting of-   ethyl    2-[4-(3-bromophenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate    (Example 1),-   2-[4-(3-bromophenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 2),-   ethyl 1-cyclohexyl-2-(4-hydroxyphenyl)benzimidazole-5-carboxylate    (Example 3),-   ethyl    2-[4-(2-bromo-5-chlorobenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate    (Example 4),-   ethyl    2-{4-[2-(4-chlorophenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate    (Example 5),-   2-{4-[2-(4-chlorophenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 6),-   ethyl    2-[4-(2-bromo-5-methoxybenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate    (Example 7),-   ethyl    2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate    (Example 8),-   2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 9),-   ethyl    1-cyclohexyl-2-{4-[(E)-2-phenylvinyl]phenyl}benzimidazole-5-carboxylate    (Example 10),-   1-cyclohexyl-2-{4-[(E)-2-phenylvinyl]phenyl}benzimidazole-5-carboxylic    acid (Example 11),-   2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxylic acid    (Example 12),-   2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxamide    (Example 13),-   2-(4-benzyloxyphenyl)-5-cyano-1-cyclopentylbenzimidazole (Example    14),-   2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxamide oxime    (Example 15),-   ethyl    1-cyclohexyl-2-{4-[{4-(4-fluorophenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylate    (Example 16),-   1-cyclohexyl-2-{4-[{4-(4-fluorophenyl)-2-methyl-5-thiazolyl}-methoxy]phenyl}benzimidazole-5-carboxylic    acid (Example 17),-   ethyl    1-cyclohexyl-2-(2-fluoro-4-hydroxyphenyl)benzimidazole-5-carboxylate    (Example 18),-   ethyl    2-{4-[bis(3-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate    (Example 19),-   2-{4-[bis(3-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 20),-   ethyl 1-cyclopentyl-2-(4-nitrophenyl)benzimidazole-5-carboxylate    (Example 21),-   ethyl 2-(4-aminophenyl)-1-cyclopentylbenzimidazole-5-carboxylate    (Example 22),-   ethyl    2-(4-benzoylaminophenyl)-1-cyclopentylbenzimidazole-5-carboxylate    (Example 23),-   2-(4-benzoylaminophenyl)-1-cyclopentylbenzimidazole-5-carboxylic    acid (Example 24),-   ethyl    2-{4-[3-(3-chlorophenyl)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate    (Example 25),-   2-{4-[3-(3-chlorophenyl)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 26),-   ethyl    2-[4-(3-acetoxyphenyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate    (Example 27),-   ethyl    1-cyclohexyl-2-[4-(3-hydroxyphenyloxy)phenyl]-benzimidazole-5-carboxylate    (Example 28),-   ethyl    1-cyclohexyl-2-{4-[3-(4-pyridylmethoxy)phenyloxy]phenyl}-benzimidazole-5-carboxylate    (Example 29),-   1-cyclohexyl-2-{4-[3-(4-pyridylmethoxy)phenyloxy]phenyl}-benzimidazole-5-carboxylic    acid (Example 30),-   2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole (Example 31),-   ethyl 2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxylate    (Example 32),-   2-(4-benzyloxyphenyl)-1-cyclopentyl-N,N-dimethylbenzimidazole-5-carboxamide    (Example 33),-   2-(4-benzyloxyphenyl)-1-cyclopentyl-N-methoxy-N-methylbenzimidazole-5-carboxamide    (Example 34),-   2-(4-benzyloxyphenyl)-1-cyclopentyl-5-(1-hydroxy-1-methylethyl)benzimidazole    (Example 35),-   5-acetyl-2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole (Example    36),-   2-(4-benzyloxyphenyl)-1-cyclopentyl-N-(2-dimethylaminoethyl)-benzimidazole-5-carboxamide    dihydrochloride (Example 37),-   2-(4-benzyloxyphenyl)-1-cyclopentyl-5-nitrobenzimidazole (Example    38),-   5-amino-2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole    hydrochloride (Example 39),-   5-acetylamino-2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole    (Example 40),-   2-(4-benzyloxyphenyl)-1-cyclopentyl-5-methanesulfonyl-aminobenzimidazole    (Example 41),-   5-sulfamoyl-2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole    (Example 42),-   2-[4-(4-tert-butylbenzyloxy)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic    acid (Example 43),-   2-[4-(4-carboxybenzyloxy)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic    acid (Example 44),-   2-[4-(4-chlorobenzyloxy)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic    acid (Example 45),-   2-{4-[(2-chloro-5-thienyl)methoxy]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic    acid (Example 46),-   1-cyclopentyl-2-[4-(4-trifluoromethylbenzyloxy)phenyl]-benzimidazole-5-carboxylic    acid (Example 47),-   1-cyclopentyl-2-[4-(4-methoxybenzyloxy)phenyl]benzimidazole-5-carboxylic    acid (Example 48),-   1-cyclopentyl-2-[4-(4-pyridylmethoxy)phenyl]benzimidazole-5-carboxylic    acid hydrochloride (Example 49),-   1-cyclopentyl-2-[4-(4-methylbenzyloxy)phenyl]benzimidazole-5-carboxylic    acid (Example 50),-   1-cyclopentyl-2-{4-[(3,5-dimethyl-4-isoxazolyl)methoxy]phenyl}-benzimidazole-5-carboxylic    acid (Example 51),-   1-cyclopentyl-2-(4-hydroxyphenyl)benzimidazole-5-carboxylic acid    (Example 52),-   [2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazol-5-yl]-carbonylaminoacetic    acid (Example 53),-   2-[4-(2-chlorobenzyloxy)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic    acid (Example 54),-   2-[4-(3-chlorobenzyloxy)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic    acid (Example 55),-   2-(4-benzyloxyphenyl)-3-cyclopentylbenzimidazole-5-carboxylic acid    (Example 56),-   2-[4-(benzenesulfonylamino)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic    acid (Example 57),-   1-cyclopentyl-2-[4-(3,5-dichlorophenylcarbonylamino)phenyl]-benzimidazole-5-carboxylic    acid (Example 58),-   2-{4-[(4-chlorophenyl)carbonylamino]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic    acid (Example 59),-   2-{4-[(4-tert-butylphenyl)carbonylamino]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic    acid (Example 60),-   2-{4-[(4-benzyloxyphenyl)carbonylamino]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic    acid (Example 61),-   trans-4-[2-(4-benzyloxyphenyl)-5-carboxybenzimidazol-1-yl]cyclohexan-1-ol    (Example 62),-   trans-1-[2-(4-benzyloxyphenyl)-5-carboxybenzimidazol-1-yl]-4-methoxycyclohexane    (Example 63),-   2-(4-benzyloxyphenyl)-5-carboxymethyl-1-cyclopentylbenzimidazole    (Example 64),-   2-[1-benzyloxycarbonyl-4-piperidyl]-1-cyclopentylbenzimidazole-5-carboxylic    acid (Example 65),-   2-[(4-cyclohexylphenyl)carbonylamino]-1-cyclopentylbenzimidazole-5-carboxylic    acid (Example 66),-   1-cyclopentyl-2-[4-(3,5-dichlorobenzyloxy)phenyl]benzimidazole-5-carboxylic    acid (Example 67),-   1-cyclopentyl-2-[4-(3,4-dichlorobenzyloxy)phenyl]benzimidazole-5-carboxylic    acid (Example 68),-   1-cyclopentyl-2-[4-(phenylcarbamoylamino)phenyl]benzimidazole-5-carboxylic    acid (Example 69),-   1-cyclopentyl-2-[4-(diphenylmethoxy)phenyl]benzimidazole-5-carboxylic    acid (Example 70),-   1-cyclopentyl-2-(4-phenethyloxyphenyl)benzimidazole-5-carboxylic    acid (Example 71),-   trans-1-[2-(4-benzyloxyphenyl)-5-carboxybenzimidazol-1-yl]-4-tert-butylcyclohexane    (Example 72),-   2-(4-benzyloxyphenyl)-5-carboxymethoxy-1-cyclopentylbenzimidazole    (Example 73),-   2-(4-benzylaminophenyl)-1-cyclopentylbenzimidazole-5-carboxylic acid    (Example 74),-   2-[4-(N-benzenesulfonyl-N-methylamino)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic    acid (Example 75),-   2-[4-(N-benzyl-N-methylamino)phenyl]-1-cyclopentylbenzimidazole-5-carboxylic    acid (Example 76),-   1-cyclohexyl-2-(4-phenethylphenyl)benzimidazole-5-carboxylic acid    (Example 77),-   2-(1-benzyl-4-piperidyl)-1-cyclopentylbenzimidazole-5-carboxylic    acid (Example 78),-   2-(1-benzoyl-4-piperidyl)-1-cyclopentylbenzimidazole-5-carboxylic    acid (Example 79),-   1-cyclopentyl-2-[1-(p-toluenesulfonyl)-4-piperidyl]-benzimidazole-5-carboxylic    acid (Example 80),-   1-cyclohexyl-2-[4-(3,5-dichlorobenzyloxy)phenyl]benzimidazole-5-carboxylic    acid (Example 81),-   1-cyclohexyl-2-[4-(diphenylmethoxy)phenyl]benzimidazole-5-carboxylic    acid (Example 82),-   1-cyclohexyl-2-[4-(3,5-di-tert-butylbenzyloxy)phenyl]-benzimidazole-5-carboxylic    acid (Example 83),-   2-(4-benzyloxyphenyl)-1-(4-methylcyclohexyl)benzimidazole-5-carboxylic    acid (Example 84),-   1-cyclohexyl-2-{4-[2-(2-naphthyl)ethoxy]phenyl}benzimidazole-5-carboxylic    acid (Example 85),-   1-cyclohexyl-2-[4-(1-naphthyl)methoxyphenyl]benzimidazole-5-carboxylic    acid (Example 86),-   1-cyclohexyl-2-[4-(dibenzylamino)phenyl]benzimidazole-5-carboxylic    acid (Example 87),-   2-[4-(2-biphenylylmethoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 88),-   2-(4-benzyloxyphenyl)-1-cyclohexylbenzimidazole-5-carboxylic acid    (Example 89),-   1-cyclohexyl-2-[4-(dibenzylmethoxy)phenyl]benzimidazole-5-carboxylic    acid (Example 90),-   2-(4-benzoylmethoxyphenyl)-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 91),-   2-(4-benzyl-1-piperazinyl)-1-cyclohexylbenzimidazole-5-carboxylic    acid dihydrochloride (Example 92),-   1-cyclohexyl-2-[4-(3,3-diphenylpropyloxy)phenyl]benzimidazole-5-carboxylic    acid (Example 93),-   2-[4-(3-chloro-6-phenylbenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 94),-   2-(4-benzyloxypiperidino)-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 95),-   1-cyclohexyl-2-{4-[2-(phenoxy)ethoxy]phenyl}benzimidazole-5-carboxylic    acid (Example 96),-   1-cyclohexyl-2-[4-(3-phenylpropyloxy)phenyl]benzimidazole-5-carboxylic    acid (Example 97),-   1-cyclohexyl-2-[4-(5-phenylpentyloxy)phenyl]benzimidazole-5-carboxylic    acid (Example 98),-   2-(3-benzyloxy-5-isoxazolyl)-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 99),-   2-(2-benzyloxy-5-pyridyl)-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 100),-   1-cyclohexyl-2-{4-[2-(3,4,5-trimethoxyphenyl)ethoxy]phenyl}-benzimidazole-5-carboxylic    acid (Example 101),-   2-(4-benzyloxyphenyl)-1-(4,4-dimethylcyclohexyl)benzimidazole-5-carboxylic    acid (Example 102),-   1-cyclohexyl-2-{4-[2-(1-naphthyl)ethoxy]phenyl}benzimidazole-5-carboxylic    acid (Example 103),-   2-[4-(2-benzyloxyphenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 104),-   2-[4-(3-benzyloxyphenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 105),-   1-cyclohexyl-2-[4-(2-hydroxyphenoxy)phenyl]benzimidazole-5-carboxylic    acid (Example 106),-   1-cyclohexyl-2-[4-(3-hydroxyphenoxy)phenyl]benzimidazole-5-carboxylic    acid (Example 107),-   1-cyclohexyl-2-[4-(2-methoxyphenoxy)phenyl]benzimidazole-5-carboxylic    acid (Example 108),-   1-cyclohexyl-2-[4-(3-methoxyphenoxy)phenyl]benzimidazole-5-carboxylic    acid (Example 109),-   1-cyclohexyl-2-[4-(2-propoxyphenoxy)phenyl]benzimidazole-5-carboxylic    acid (Example 110),-   1-cyclohexyl-2-[4-(3-propoxyphenoxy)phenyl]benzimidazole-5-carboxylic    acid (Example 111),-   1-cyclohexyl-2-{4-[2-(3-methyl-2-butenyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic    acid (Example 112),-   1-cyclohexyl-2-{4-[3-(3-methyl-2-butenyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic    acid (Example 113),-   1-cyclohexyl-2-[4-(2-isopentyloxyphenoxy)phenyl]benzimidazole-5-carboxylic    acid (Example 114),-   1-cyclohexyl-2-[4-(3-isopentyloxyphenoxy)phenyl]benzimidazole-5-carboxylic    acid (Example 115),-   1-cyclohexyl-2-{4-[2-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)ethoxy]phenyl}benzimidazole-5-carboxylic    acid (Example 116),-   1-cyclohexyl-2-{4-[2-(4-trifluoromethylphenyl)benzyloxy]-phenyl}benzimidazole-5-carboxylic    acid (Example 117),-   2-{4-[bis(4-chlorophenyl)methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 118),-   1-cyclohexyl-2-{4-[2-(4-methoxyphenyl)ethoxy]phenyl}-benzimidazole-5-carboxylic    acid (Example 119),-   1-cyclohexyl-2-{4-[2-(2-methoxyphenyl)ethoxy]phenyl}-benzimidazole-5-carboxylic    acid (Example 120),-   1-cyclohexyl-2-{4-[2-(3-methoxyphenyl)ethoxy]phenyl}-benzimidazole-5-carboxylic    acid (Example 121),-   2-(4-benzyloxyphenyl)-1-cycloheptylbenzimidazole-5-carboxylic acid    (Example 122),-   1-cyclohexyl-2-[4-(2-phenethyloxyphenoxy)phenyl]benzimidazole-5-carboxylic    acid (Example 123),-   1-cyclohexyl-2-[4-(3-phenethyloxyphenoxy)phenyl]benzimidazole-5-carboxylic    acid (Example 124),-   1-cyclohexyl-2-[4-(2,2-diphenylethoxy)phenyl]benzimidazole-5-carboxylic    acid (Example 125),-   2-(4-benzyloxyphenyl)-1-(3-cyclohexenyl)benzimidazole-5-carboxylic    acid (Example 126),-   cis-1-[2-(4-benzyloxyphenyl)-5-carboxybenzimidazol-1-yl]-4-fluorocyclohexane    (Example 127),-   1-cyclohexyl-2-[4-(2-phenoxyphenoxy)phenyl]benzimidazole-5-carboxylic    acid (Example 128),-   1-cyclohexyl-2-[4-(3-phenoxyphenoxy)phenyl]benzimidazole-5-carboxylic    acid (Example 129),-   2-{4-[(2R)-2-benzyloxycarbonylamino-2-phenylethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 130),-   1-cyclohexyl-2-{2-fluoro-4-[2-(4-trifluoromethylphenyl)-benzyloxy]phenyl}benzimidazole-5-carboxylic    acid (Example 131),-   2-[4-(4-benzyloxyphenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 132),-   2-{4-[bis(4-methylphenyl)methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 133),-   2-{4-[bis(4-fluorophenyl)methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 134),-   1-cyclohexyl-6-methoxy-2-[4-(3-phenylpropoxy)phenyl]-benzimidazole-5-carboxylic    acid (Example 135),-   1-cyclohexyl-6-hydroxy-2-[4-(3-phenylpropoxy)phenyl]-benzimidazole-5-carboxylic    acid (Example 136),-   1-cyclohexyl-6-methyl-2-[4-(3-phenylpropoxy)phenyl]-benzimidazole-5-carboxylic    acid (Example 137),-   2-{4-[2-(2-benzyloxyphenyl)ethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 138),-   2-{4-[2-(3-benzyloxyphenyl)ethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 139),-   2-[4-(2-carboxymethyloxyphenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 140),-   2-[4-(3-carboxymethyloxyphenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 141),-   2-{4-[3-chloro-6-(4-methylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 142),-   2-{4-[3-chloro-6-(4-methoxyphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 143),-   1-cyclohexyl-2-{2-methyl-4-[2-(4-trifluoromethylphenyl)-benzyloxy]phenyl}benzimidazole-5-carboxylic    acid (Example 144),-   2-{4-[2-(4-tert-butylphenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 145),-   2-{4-(3-chloro-6-phenylbenzyloxy)-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 146),-   2-{4-[3-chloro-6-(3,5-dichlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 147),-   2-{4-[bis(4-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 148),-   2-{4-(4-benzyloxyphenoxy)-2-chlorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 149),-   2-{4-(4-benzyloxyphenoxy)-2-trifluoromethylphenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 150),-   2-{4-[3-chloro-6-(2-trifluoromethylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 151),-   2-{4-[(2R)-2-amino-2-phenylethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 152),-   2-[4-(2-biphenylyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 153),-   2-[4-(3-biphenylyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 154),-   2-{4-[2-{1    (1-tert-butoxycarbonyl-4-piperidyl)methoxy}phenoxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 155),-   2-{4-[3-{(1-tert-butoxycarbonyl-4-piperidyl)methoxy}phenoxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 156),-   2-{4-[3-chloro-6-(3,4,5-trimethoxyphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 157),-   2-{4-[2-(2-biphenylyl)ethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 158),-   2-[4-(2-biphenylylmethoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 159),-   1-cyclohexyl-2-{4-[2-(4-piperidylmethoxy)phenoxy]phenyl}-benzimidazole-5-carboxylic    acid hydrochloride (Example 160),-   1-cyclohexyl-2-{4-[3-(4-piperidylmethoxy)phenoxy]phenyl}-benzimidazole-5-carboxylic    acid hydrochloride (Example 161),-   2-{4-[(2R)-2-acetylamino-2-phenylethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 162),-   1-cyclohexyl-2-{4-[3-(4-methyl-3-pentenyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic    acid (Example 163),-   1-cyclohexyl-2-{4-[3-(3-methyl-3-butenyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic    acid (Example 164),-   2-{4-[{(2S)-1-benzyl-2-pyrrolidinyl}methoxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic    acid hydrochloride (Example 165),-   2-{4-[3-chloro-6-(4-methylthiophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 166),-   2-{4-[3-chloro-6-(4-methanesulfonylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 167),-   2-{4-[3-chloro-6-(2-thienyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 168),-   2-{4-[3-chloro-6-(3-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 169),-   2-{4-[3-chloro-6-(3-pyridyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 170),-   2-{4-[3-chloro-6-(4-fluorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 171),-   2-[4-(4-benzyloxyphenoxy)-3-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 172),-   2-[4-(2-bromo-5-chlorobenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 173),-   2-{4-[3-chloro-6-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 174),-   2-{4-[2-{(1-acetyl-4-piperidyl)methoxy}phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 175),-   2-{4-[3-{(1-acetyl-4-piperidyl)methoxy}phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 176),-   1-cyclohexyl-2-{4-[3-(2-propynyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic    acid (Example 177),-   1-cyclohexyl-2-{4-[3-(3-pyridylmethoxy)phenoxy]phenyl}-benzimidazole-5-carboxylic    acid (Example 178),-   2-(4-benzyloxy-2-methoxyphenyl)-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 179),-   2-[4-(2-bromo-5-methoxybenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 180),-   2-[4-(carboxydiphenylmethoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 181),-   2-{4-[2-(4-chlorophenyl)-5-nitrobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 182),-   2-{4-[3-acetylamino-6-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 183),-   2-{4-[2-(4-carboxyphenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 184),-   2-{4-[{(2S)-1-benzyloxycarbonyl-2-pyrrolidinyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 185),-   2-{2-chloro-4-[2-(4-trifluoromethylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 186),-   1-cyclohexyl-2-{4-[3-(2-pyridylmethoxy)phenoxy]phenyl}-benzimidazole-5-carboxylic    acid (Example 187),-   2-{4-[2-(4-chlorophenyl)-5-fluorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 188),-   2-{4-[3-carboxy-6-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 189),-   2-{4-[3-carbamoyl-6-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 190),-   1-cyclohexyl-2-{4-[2-(dimethylcarbamoylmethoxy)phenoxy]-phenyl}benzimidazole-5-carboxylic    acid (Example 191),-   1-cyclohexyl-2-{4-[2-(piperidinocarbonylmethoxy)phenoxy]-phenyl}benzimidazole-5-carboxylic    acid (Example 192),-   2-{4-[{(2S)-1-benzenesulfonyl-2-pyrrolidinyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 193),-   2-{4-[{(2S)-1-benzoyl-2-pyrrolidinyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 194),-   2-{4-[2-(4-carbamoylphenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 195),-   1-cyclohexyl-2-{4-[3-(dimethylcarbamoylmethoxy)phenoxy]-phenyl}benzimidazole-5-carboxylic    acid (Example 196),-   1-cyclohexyl-2-{4-[3-(piperidinocarbonylmethoxy)phenoxy]-phenyl}benzimidazole-5-carboxylic    acid (Example 197),-   1-cyclohexyl-2-{4-[3-{(1-methanesulfonyl-4-piperidyl)methoxy}-phenoxy]phenyl}benzimidazole-5-carboxylic    acid (Example 198),-   1-cyclohexyl-2-{4-[{2-methyl-5-(4-chlorophenyl)-4-oxazolyl}-methoxy]phenyl}benzimidazole-5-carboxylic    acid (Example 199),-   2-{4-[3-(3-chlorobenzyloxy)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 200),-   2-{4-[3-(4-chlorobenzyloxy)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 201),-   1-cyclohexyl-2-{4-[3-(4-fluorobenzyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic    acid (Example 202),-   1-cyclohexyl-2-{4-[{(2S)-1-(4-nitrophenyl)-2-pyrrolidinyl}-methoxy]phenyl}benzimidazole-5-carboxylic    acid (Example 203),-   1-cyclohexyl-2-{4-[{(2S)-1-phenyl-2-pyrrolidinyl}methoxy]-phenyl}benzimidazole-5-carboxylic    acid hydrochloride (Example 204),-   2-{4-[{(2S)-1-(4-acetylaminophenyl)-2-pyrrolidinyl}methoxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 205),-   2-{4-[{5-(4-chlorophenyl)-2-methyl-4-thiazolyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 206),-   2-{4-[bis(3-fluorophenyl)methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 207),-   1-cyclohexyl-2-{4-[2-(4-chlorophenyl)-3-nitrobenzyloxy]phenyl}-benzimidazole-5-carboxylic    acid (Example 208),-   1-cyclohexyl-2-{4-[3-(4-tetrahydropyranyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic    acid (Example 209),-   1-cyclohexyl-2-{4-[3-(4-trifluoromethylbenzyloxy)phenoxy]phenyl}-benzimidazole-5-carboxylic    acid (Example 210),-   1-cyclohexyl-2-{4-[3-{(1-methyl-4-piperidyl)methoxy}phenoxy]-phenyl}benzimidazole-5-carboxylic    acid (Example 211),-   2-{4-[3-(4-tert-butylbenzyloxy)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 212),-   2-{4-[3-(2-chlorobenzyloxy)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 213),-   1-cyclohexyl-2-{4-[3-(3-pyridyl)phenoxy]phenyl}benzimidazole-5-carboxylic    acid (Example 214),-   2-{4-[3-(4-chlorophenyl)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 215),-   1-cyclohexyl-2-{4-[3-(4-methoxyphenyl)phenoxy]phenyl}-benzimidazole-5-carboxylic    acid (Example 216),-   1-cyclohexyl-2-{4-[{4-(4-methanesulfonylphenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylic    acid (Example 217),-   2-{4-[{4-(4-chlorophenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 218),-   2-{4-[1-(4-chlorobenzyl)-3-piperidyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 219),-   1-cyclohexyl-2-{4-[3-{(2-methyl-4-thiazolyl)methoxy}phenoxy]-phenyl}benzimidazole-5-carboxylic    acid (Example 220),-   1-cyclohexyl-2-{4-[3-{(2,4-dimethyl-5-thiazolyl)methoxy}phenoxy]-phenyl}benzimidazole-5-carboxylic    acid (Example 221),-   1-cyclohexyl-2-{4-[3-(3,5-dichlorophenyl)phenoxy]phenyl}-benzimidazole-5-carboxylic    acid (Example 222),-   2-{4-[1-(4-chlorobenzyl)-4-piperidyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 223),-   2-{4-[3-(4-chlorobenzyloxy)piperidino]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 224),-   2-{4-[4-carbamoyl-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 225),-   2-{4-[4-(4-chlorobenzyloxy)piperidino]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 226),-   2-{4-[3-{(2-chloro-4-pyridyl)methoxy}phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 227),-   2-{4-[{(2S)-1-(4-dimethylcarbamoylphenyl)-2-pyrrolidinyl}-methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 228),-   2-{4-[2-(4-chlorophenyl)-5-ethoxycarbonylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 229),-   1-cyclohexyl-2-[4-(3-trifluoromethylphenoxy)phenyl]-benzimidazole-5-carboxylic    acid (Example 230),-   1-cyclohexyl-2-{4-[{4-(4-dimethylcarbamoylphenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylic    acid (Example 231),-   2-{4-[2-(4-chlorophenyl)-5-dimethylcarbamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 232),-   2-{4-[{4-(4-chlorophenyl)-2-methyl-5-pyrimidinyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 233),-   2-{4-[{2-(4-chlorophenyl)-3-pyridyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid dihydrochloride (Example 234),-   2-{4-[{3-(4-chlorophenyl)-2-pyridyl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 235),-   2-{4-[2-(3-chlorophenyl)-4-methylamino-1,3,5-triazin-6-yloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid trifluoroacetate (Example 236),-   2-{4-[2-(4-chlorophenyl)-4-(5-tetrazolyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 237),-   2-[4-(4-benzyloxy-6-pyrimidinyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 238),-   1-cyclohexyl-2-{4-[4-(4-pyridylmethoxy)-6-pyrimidinyloxy]phenyl}-benzimidazole-5-carboxylic    acid (Example 239),-   2-{4-[4-(3-chlorophenyl)-6-pyrimidinyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 240),-   methyl    2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate    (Example 241),-   2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic    acid hydrochloride (Example 242),-   ethyl    2-{4-[3-(4-chlorophenyl)pyridin-2-ylmethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate    (Example 243),-   methyl    2-[4-(2-bromo-5-tert-butoxycarbonylbenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate    (Example 244),-   methyl    2-{4-[5-tert-butoxycarbonyl-2-(4-chlorophenyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylate    (Example 245),-   methyl    2-{4-[5-carboxy-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate    hydrochloride (Example 246),-   methyl    2-{4-[2-(4-chlorophenyl)-5-methylcarbamoylbenzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylate    (Example 247),-   2-{4-[2-(4-chlorophenyl)-5-methylcarbamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 248),-   2-{4-[3-(tert-butylsulfamoyl)-6-(4-chlorophenyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 249),-   2-{4-[2-(4-chlorophenyl)-5-sulfamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid trifluoroacetate (Example 250),-   2-(4-benzyloxycyclohexyl)-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 251),-   2-[2-(2-biphenylyloxymethyl)-5-thienyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 252),-   2-[2-(2-biphenylyloxymethyl)-5-furyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 253),-   1-cyclohexyl-2-{4-[{4-(4-fluorophenyl)-2-hydroxymethyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylic    acid (Example 254),-   1-cyclohexyl-2-{4-[{4-(4-carboxyphenyl)-2-methyl-5-thiazolyl}-methoxy]phenyl}benzimidazole-5-carboxylic    acid hydrochloride (Example 255),-   1-cyclohexyl-2-{2-fluoro-4-[4-fluoro-2-(3-fluorobenzoyl)-benzyloxy]phenyl}benzimidazole-5-carboxylic    acid (Example 256),-   2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-sulfonic    acid (Example 257),-   2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-3-cyclohexylbenzimidazole-4-carboxylic    acid (Example 258),-   1-cyclohexyl-2-{4-[3-dimethylcarbamoyl-5-(4-pyridylmethoxy)-phenoxy]phenyl}benzimidazole-5-carboxylic    acid dihydrochloride (Example 259),-   1-cyclohexyl-2-{4-[3-carboxy-5-(4-pyridylmethoxy)phenoxy]-phenyl}benzimidazole-5-carboxylic    acid dihydrochloride (Example 260),-   2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-4-carboxylic    acid (Example 261),-   2-{4-[3-carbamoyl-6-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 262),-   2-{4-[{2-(4-carboxyphenyl)-3-pyridyl    methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid (Example    263),-   2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-(4-tetrahydrothiopyranyl)benzimidazole-5-carboxylic    acid (Example 264),-   2-{4-[2-(4-chlorophenyl)-5-dimethylcarbamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 265),-   1-cyclohexyl-2-{4-[3-dimethylcarbamoyl-6-(4-trifluoromethylphenyl)benzyloxy]phenyl}benzimidazole-5-carboxylic    acid hydrochloride (Example 266),-   1-cyclohexyl-2-{4-[3-dimethylcarbamoyl-6-(4-methylthiophenyl)-benzyloxy]phenyl}benzimidazole-5-carboxylic    acid hydrochloride (Example 267),-   2-{4-[2-(4-chlorophenyl)-5-methylcarbamoylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 268),-   2-{4-[2-(4-chlorophenyl)-5-dimethylcarbamoylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 269),-   2-{4-[3-carbamoyl-6-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 270),-   2-{4-[3-dimethylcarbamoyl-6-(4-methanesulfonylphenyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 271),-   2-{4-[3-dimethylcarbamoyl-6-(3-pyridyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid dihydrochloride (Example 272),-   2-{4-[3-dimethylcarbamoyl-6-(4-dimethylcarbamoylphenyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 273),-   2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-(1-oxo-4-tetrahydrothiopyranyl)benzimidazole-5-carboxylic    acid (Example 274),-   2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-(1,1-dioxo-4-tetrahydrothiopyranyl)benzimidazole-5-carboxylic    acid (Example 275),-   2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy)-2-fluorophenyl}-1-(4-tetrahydrothiopyranyl)benzimidazole-5-carboxylic    acid (Example 276),-   2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]-2-fluorophenyl}-1-(1-oxo-4-tetrahydrothiopyranyl)benzimidazole-5-carboxylic    acid (Example 277),-   2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]-2-fluorophenyl}-1-(1,1-dioxo-4-tetrahydrothiopyranyl)benzimidazole-5-carboxylic    acid (Example 278),-   2-{4-[2-(4-chlorophenyl)-5-dimethylsulfamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 279),-   2-{4-[2-(4-chlorophenyl)-5-methanesulfonylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 280),-   methyl    2-{4-[5-carboxy-2-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate    hydrochloride (Example 281),-   2-{4-[2-(4-chlorophenyl)-5-dimethylaminobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid dihydrochloride (Example 282),-   2-{4-[2-(4-chlorophenyl)-5-methanesulfonylaminobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 283),-   2-{4-[2-(4-chlorophenyl)-5-diethylcarbamoylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 284),-   2-{4-[2-(4-chlorophenyl)-5-isopropylcarbamoylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 285),-   2-{4-[2-(4-chlorophenyl)-5-piperidinocarbonylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 286),-   2-{4-[2-(4-chlorophenyl)-5-(1-pyrrolidinyl)carbonylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 287),-   2-{4-[2-(4-chlorophenyl)-5-(2-hydroxyethyl)carbamoylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 288),-   2-{4-(2-(4-chlorophenyl)-5-(4-hydroxypiperidino)-carbonylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 289),-   2-{4-[2-(4-chlorophenyl)-5-morpholinocarbonylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 290),-   2-{4-[2-(4-chlorophenyl)-5-thiomorpholinocarbonylbenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 291),-   2-{4-[3-(carboxymethylcarbamoyl)-6-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 292),-   2-{4-[2-{4-(2-carboxyethyl)phenyl}-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 293),-   2-{4-[3-chloro-6-(4-hydroxymethylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 294),-   2-{4-[3-chloro-6-(4-methoxymethylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 295),-   2-{4-[2-(3-carboxyphenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 296),-   2-{4-[2-(4-chlorophenyl)-5-methylthiobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 297),-   2-{4-[2-(4-chlorophenyl)-5-methylsulfinylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 298),-   2-{4-[2-(4-chlorophenyl)-5-cyanobenzyloxy]phenyl}-1-cyclohexyl-benzimidazole-5-carboxylic    acid hydrochloride (Example 299),-   2-{4-[bis(3-pyridyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 300),-   2-{4-[bis(4-dimethylcarbamoylphenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 301),-   sodium    2-{4-[2-thienyl-3-thienylmethoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate    (Example 302),-   methyl    2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate    (Example 303),-   sodium    2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate    (Example 304),-   2-{4-[5-carboxy-2-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 305),-   2-{4-[2-(4-carboxyphenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 306),-   2-{4-[2-(4-carbamoylphenyl)-5-(dimethylcarbamoyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 307),-   2-{4-[5-amino-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 308),-   2-{4-[5-(4-chlorophenyl)-2-methoxybenzylsulfinyl]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 309),-   2-{4-[5-(4-chlorophenyl)-2-methoxybenzylsulfonyl]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 310),-   2-{4-[2-(4-chlorophenyl)-5-methoxybenzylthio]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 311),-   2-{4-[bis(4-carboxyphenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 312),-   2-[4-(phenyl}-3-pyridylmethoxy)-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 313),-   methyl    2-{4-[2-(4-chlorophenyl)-5-(methylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate    (Example 314),-   2-{4-[5-chloro-2-(4-pyridyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 315),-   2-{4-[2-(4-chlorophenyl)-5-(benzylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 316),-   2-{4-[2-(4-chlorophenyl)-5-(cyclohexylmethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 317),-   2-{4-[2-(4-chlorophenyl)-5-(4-pyridylmethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid dihydrochloride (Example 318),-   2-{4-[2-(4-chlorophenyl)-5-(N-benzyl-N-methylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 319),-   2-{4-[5-dimethylaminocarbonyl-2-(4-pyridyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid dihydrochloride (Example 320),-   2-{4-[2-(4-chlorophenyl)-5-(4-methylpiperazin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid dihydrochloride (Example 321),-   2-{4-[2-(4-chlorophenyl)-5-[{N-(3-pyridylmethyl)carbamoyl}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid dihydrochloride (Example 322),-   2-{4-[2-(4-chlorophenyl)-5-[{N-(2-pyridylmethyl)carbamoyl}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid dihydrochloride (Example 323),-   2-{4-[2-(4-chlorophenyl)-5-(cyclohexylcarbamoyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 324),-   2-{4-[2-(4-chlorophenyl)-5-(2-pyridin-4-ylethylcarbamoyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid dihydrochloride (Example 325),-   2-{4-[(4-fluorophenyl){4-(dimethylaminocarbonyl)phenyl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 326),-   2-{4-[(4-fluorophenyl)(4-carboxyphenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 327),-   2-{4-[2-(4-chlorophenyl)-5-(4-oxopiperidinocarbonyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 328),-   2-{4-[2-(4-chlorophenyl)-5-hydroxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 329),-   2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 330),-   2-{4-[2-(4-chlorophenyl)-5-(N-isopropyl-N-methylcarbamoyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 331),-   2-{4-[2-(4-chlorophenyl)-5-(phenylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 332),-   2-{4-[2-(4-chlorophenyl)-5-(4-methoxypiperidinocarbonyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 333),-   2-{4-[2-(4-chlorophenyl)-5-(3-hydroxypropyloxy)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 334),-   2-{4-[2-(4-chlorophenyl)-5-(2-hydroxyethoxy)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 335),-   methyl    2-[4-(2-bromo-5-nitrobenzyloxy)-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate    (Example 336),-   methyl    2-[4-{2-(4-chlorophenyl)-5-nitrobenzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate    (Example 337),-   methyl    2-[4-{5-amino-2-(4-chlorophenyl)benzyloxy-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate    (Example 338),-   methyl    2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate    (Example 339),-   2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 340),-   2-{4-[2-(4-chlorophenyl)-5-(4-methylpiperidin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 341),-   2-{4-[5-acetyl-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 342),-   2-{4-[2-(4-chlorophenyl)-5-{(4-hydroxypiperidin-1-ylcarbonyl)-methoxy    benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid    (Example 343),-   2-{4-[2-(4-chlorophenyl)-5-(2-methoxyethoxy)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 344),-   2-{4-[2-(4-chlorophenyl)-5-{2-(2-methoxyethoxy)ethoxy}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 345),-   2-{4-[2-(4-chlorophenyl)-5-(isobutylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 346),-   2-{4-[2-(4-chlorophenyl)-5-(2-methylthiazol-4-yl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 347),-   2-{4-[2-(4-chlorophenyl)-5-(3,4-dihydroxypiperidin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 348),-   2-{4-[2-(4-chlorophenyl)-5-(3-methyl-1,2,4-oxadiazol-5-yl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 349),-   2-{4-[2-(4-chlorophenyl)-4-(isopropylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 350),-   2-{4-[2-(4-chlorophenyl)-4-(piperidinocarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 351),-   2-{4-[2-(4-chlorophenyl)-5-{(1-hydroxy-2-methylpropan-2-yl)carbamoyl}benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 352),-   2-{4-[2-(4-chlorophenyl)-5-(4,4-dimethyl-2-oxazolin-2-yl)}benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid dihydrochloride (Example 353),-   2-{4-[2-(4-chlorophenyl)-4-(4-hydroxypiperidin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 354),-   2-{4-[2-(4-chlorophenyl)-4-{(2-hydroxyethyl)carbamoyl}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 355),-   2-{4-[2-(4-chlorophenyl)-4-{(4-pyridylmethyl)carbamoyl}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 356),-   2-{4-[2-(4-chlorophenyl)-4-(dimethylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 357),-   2-{4-[5-(2-aminothiazol-4-yl)-2-(4-chlorophenyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid dihydrochloride (Example 358),-   2-{4-[2-(4-chlorophenyl)-5-(4-hydroxypiperidin-1-ylsulfonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 359),-   2-{4-[5-(dimethylcarbamoyl)-2-(4-fluorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 360),-   2-{4-[5-(dimethylcarbamoyl)-2-(3-fluorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 361),-   2-{4-[2-(5-chlorothiophen-2-yl)-5-(dimethylcarbamoyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 362),-   2-{4-[2-bromo-5-(5-methyloxazol-2-yl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 363),-   2-{4-[2-bromo-5-(5-methylthiazol-2-yl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 364),-   2-{4-[2-(4-chlorophenyl)-5-(5-methyloxazol-2-yl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 365),-   2-{4-[2-(4-chlorophenyl)-5-(5-methylthiazol-2-yl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 366),-   2-{4-[2-(4-chlorophenyl)-5-tetrazol-5-ylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 367),-   2-{4-[5-chloro-2-(4-cyanophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 368),-   2-{4-[5-chloro-2-(4-tetrazol-5-ylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 369),-   2-{4-[2-(4-chlorophenyl)-5-{2-(4-hydroxypiperidin-1-yl)ethoxy}benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 370),-   2-{4-[2-(4-chlorophenyl)-5-(2-oxopiperidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 371),-   2-{4-[3-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 372),-   2-{4-[2-(4-chlorophenyl)-5-(N-hydroxyamidino)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid dihydrochloride (Example 373),-   2-{4-[2-(4-chlorophenyl)-5-(2,5-dihydro-5-oxo-4H-1,2,4-oxadiazol-3-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 374),-   2-{4-[2-(4-chlorophenyl)-5-(2-oxo-3H-1,2,3,5-oxathiadiazol-4-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 375),-   2-{4-[2-(4-chlorophenyl)-5-(2,5-dihydro-5-oxo-4H-1,2,4-thiadiazol-3-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 376),-   2-{4-[2-(4-chlorophenyl)-5-(cyclopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 377),-   2-{4-[2-(4-chlorophenyl)-5-(cyclobutylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 378),-   2-{4-[2-(4-chlorophenyl)-5-(tert-butylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 379),-   2-{4-[2-(4-chlorophenyl)-5-(isobutylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 380),-   2-{4-[2-(4-chlorophenyl)-5-{(1-hydroxypropan-2-yl)carbamoyl}-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 381),-   2-{4-[2-(4-chlorophenyl)-5-(methoxycarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 382),-   2-{4-[2-(4-chlorophenyl)-5-{(2,3-dihydroxypropyl)carbamoyl}-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 383),-   2-{4-[2-(4-chlorophenyl)-5-(N-ethyl-N-methylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 384),-   2-{4-[2-(4-chlorophenyl)-5-(N-methyl-N-propylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 385),-   2-{4-[2-(4-chlorophenyl)-5-(N-isopropyl-N-methylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 386),-   2-{4-[2-(4-chlorophenyl)-5-(2,6-dimethylpiperidin-1-ylcarbonyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 387),-   2-{4-[5-(butylcarbamoyl)-2-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 388),-   2-{4-[2-(4-chlorophenyl)-5-(propylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 389),-   2-{4-[2-(4-chlorophenyl)-5-(ethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 390),-   2-{4-[2-(4-chlorophenyl)-5-{(dimethylcarbamoyl)amino}benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 391),-   2-{4-[2-(4-chlorophenyl)-5-{(morpholinocarbonyl)amino}benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 392),-   2-{4-[2-(4-chlorophenyl)-5-ureidobenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 393),-   2-{4-[2-(4-chlorophenyl)-5-{(ethylcarbamoyl)amino}benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 394),-   2-{4-[2-(4-chlorophenyl)-5-{(isopropylcarbamoyl)amino}benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 395),-   2-{4-[2-(3,4-difluorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 396),-   2-{4-[2-(2,4-difluorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 397),-   2-{4-[2-(3,5-dichlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 398),-   2-{4-[2-(3-chloro-4-fluorophenyl)-5-(isopropylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 399),-   2-{4-[2-(3,4-dichlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 400),-   2-{4-[2-(4-chloro-2-fluorophenyl)-5-(isopropylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 401),-   2-{4-[2-(4-chloro-2-fluorophenyl)-5-(pyrrolidin-1-ylcarbonyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 402),-   2-{4-[2-(4-chloro-3-fluorophenyl)-5-(pyrrolidin-1-ylcarbonyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 403),-   2-{4-[2-(4-chloro-3-fluorophenyl)-5-(isopropylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 404),-   2-{4-[2-{4-(methylthio)    phenyl}-5-(2-oxopyrrolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 405),-   2-{4-[2-{4-(methylthio)    phenyl}-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 406),-   2-{4-[4-chloro-2-(4-chlorophenyl)-5-(1,1-dioxoisothiazolidin-2-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 407),-   2-{4-[4-chloro-2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 408),-   2-{4-[2-(4-chlorophenyl)-5-(isopropylaminosulfonyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 409),-   2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclopentylbenzimidazole-5-carboxylic    acid hydrochloride (Example 410),-   2-{4-[2-(4-chlorophenyl)-5-(4-hydroxypiperidin-1-ylcarbonyl)-benzyloxy]-2-fluorophenyl}-1-cyclopentylbenzimidazole-5-carboxylic    acid hydrochloride (Example 411),-   2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclopentylbenzimidazole-5-carboxylic    acid hydrochloride (Example 412),-   2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic    acid hydrochloride (Example 413),-   2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic    acid hydrochloride (Example 414),-   2-{4-[2-(4-chlorophenyl)-5-(4-hydroxypiperidin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic    acid hydrochloride (Example 415),-   2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]phenyl}-1-(tetrahydrothiopyran-4-yl)benzimidazole-5-carboxylic    acid hydrochloride (Example 416),-   2-{4-[2-(4-chlorophenyl)-5-(pyrrolidin-1-ylcarbonyl)benzyloxy]-phenyl}-1-(tetrahydrothiopyran-4-yl)benzimidazole-5-carboxylic    acid hydrochloride (Example 417),-   2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-(tetrahydrothiopyran-4-yl)benzimidazole-5-carboxylic    acid hydrochloride (Example 418),-   2-{4-[2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-(tetrahydrothiopyran-4-yl)benzimidazole-5-carboxylic    acid hydrochloride (Example 419),-   2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-piperidinobenzimidazole-5-carboxylic    acid hydrochloride (Example 420),-   2-{4-[2-(4-chlorophenyl)-5-(pyrrolidin-1-ylcarbonyl)benzyloxy]-2-fluorophenyl}-1-piperidinobenzimidazole-5-carboxylic    acid (Example 421),-   2-{4-[2-(4-chlorophenyl)-5-(2-imidazolin-2-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid dihydrochloride (Example 422),-   2-{4-[2-(4-chlorophenyl)-5-(2-oxooxazolidin-3-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 423),-   2-{4-[2-(4-chlorophenyl)-5-(2-oxoimidazolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 424),-   2-{4-[2-(4-chlorophenyl)-5-(2-oxazolin-2-ylamino)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid dihydrochloride (Example 425),-   2-{4-[{2-[{(dimethylcarbamoyl)methoxy}methyl]-4-(4-fluorophenyl)thiazol-5-yl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 426),-   2-{4-[{4-(4-fluorophenyl)-2-(4-hydroxypiperidin-1-ylmethyl)thiazol-5-yl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid dihydrochloride (Example 427),-   2-{4-[{4-(4-fluorophenyl)-2-[(carbamoylmethoxy)methyl]thiazol-5-yl    methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid    hydrochloride (Example 428),-   2-{4-[{4-(4-fluorophenyl)-2-(methylcarbamoyl)thiazol-5-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 429),-   2-{4-[{4-(4-fluorophenyl)-2-{(2-hydroxyethyl)carbamoyl}thiazol-5-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 430),-   2-{4-[{2-(4-fluorophenyl)-5-(dimethylcarbamoyl)thiophen-3-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 431),-   2-{4-[{2-(4-fluorophenyl)-5-(isopropylcarbamoyl)thiophen-3-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 432),-   2-{4-[{2-(4-fluorophenyl)-5-(4-hydroxypiperidin-1-ylcarbonyl)thiophen-3-yl    methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic acid    hydrochloride (Example 433),-   2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexyl-5-tetrazol-5-ylbenzimidazole    (Example 434),-   2-{4-[2-(4-carboxyphenyl)-5-chlorobenzyloxy]-2-fluorophenyl}-1-cyclohexyl-5-tetrazol-5-ylbenzimidazole    hydrochloride (Example 435),-   2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexyl-5-(2,5-dihydro-5-oxo-4H-1,2,4-oxadiazol-3-yl)benzimidazole    hydrochloride (Example 436),-   2-{4-[5-carboxy-2-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-5-cyano-1-cyclohexylbenzimidazole    (Example 437),-   2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-5-cyano-1-cyclohexylbenzimidazole    (Example 438),-   2-{4-[{N-(4-dimethylcarbamoyl)-N-(4-fluorophenyl)amino}-methyl]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 439),-   2-{5-[bis(3-fluorophenyl)methyl]-2-fluoro-4-hydroxyphenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 440),-   2-{3-[bis(3-fluorophenyl)methyl]-2-fluoro-4-hydroxyphenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 441),-   2-{4-[(3-dimethylcarbamoylphenyl)(4-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 442),-   2-{4-[{3-(4-hydroxypiperidyl-1-ylcarbonyl)phenyl}(4-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 443),-   1-{[2-{4-([4-(4-fluorophenyl)-2-methylthiazol-5-yl]methoxy)phenyl}-1-cyclohexylbenzimidazol-5-yl]carbonyl}-β-D-glucuronic    acid (Example 444),-   {[2-{4-[bis(3-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazol-5-yl]carbonyl}-β-D-glucuronic    acid (Example 445),-   2-{4-[2-(4-chlorophenyl)-5-(1,1-dioxoisothiazolidin-2-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 446),-   3-{[4-(5-aminosulfonyl-1-cyclohexylbenzimidazol-2-yl)-3-fluorophenoxy]methyl}-4-(4-chlorophenyl)-N-isopropylbenzamide    (Example 447),-   2-[4-{2-(4-chlorophenyl)-6-(isopropylaminocarbonyl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 448),-   2-[4-{2-(4-chlorophenyl)-4-fluoro-5-(1,1-dioxoisothiazolidin-2-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 449),-   2-[4-{2-(4-chlorophenyl)-5-(isopropylaminocarbonyl)benzyloxy}-2-fluorophenyl]-1-cyclohexyl-4-methoxybenzimidazole-5-carboxylic    acid hydrochloride (Example 450),-   2-[4-{2-(4-chlorophenyl)-5-(N-isopropylcarbonyl-N-methylamino)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 451),-   2-[4-{2-(4-chlorophenyl)-5-(isopropylcarbonylamino)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 452),-   2-[3-{[4-(4-fluorophenyl)-2-methylthiazol-5-yl]methyl}-4-hydroxyphenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 453),-   2-[4-{2-(4-chlorophenyl)-4-fluoro-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 454),-   2-[4-{2-(4-chlorophenyl)-5-(methylsulfonylamino)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 455),-   2-[4-{2-(4-chlorophenyl)-5-[N-methyl-N-(methylsulfonyl)amino]benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 456),-   2-[4-{[3-(4-chlorophenyl)-6-(2-oxopyrrolidin-1-yl)pyridin-2-yl]methyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 457),-   2-[4-{2-(4-chlorophenyl)-5-(acetylamino)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 458),-   2-[4-{2-(4-chlorophenyl)-5-(N-acetyl-N-ethylamino)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 459),-   2-[4-{2-(4-chlorophenyl)-5-(N-acetyl-N-propylamino)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 460),-   2-[4-{2-(4-chlorophenyl)-5-[N-ethyl-N-(methylsulfonyl)amino]-benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 461),-   2-[4-{2-(4-chlorophenyl)-5-[N-(methylsulfonyl)-N-propylamino]benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 462),-   2-[4-{2-(4-chlorophenyl)-5-(N-acetyl-N-methylamino)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 463),-   2-[4-{2-(4-chlorophenyl)-5-[N-(ethylsulfonyl)-N-methylamino]-benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 464),-   2-[4-{2-(4-chlorophenyl)-5-[N-ethyl-N-(ethylsulfonyl)amino]-benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 465),-   2-[4-{2-(4-chlorophenyl)-5-[N-(ethylcarbonyl)-N-methylamino]-benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 466),-   2-[4-{2-(4-chlorophenyl)-5-[N-ethyl-N-(ethylcarbonyl)amino]-benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 467),-   2-[4-{2-(4-chlorophenyl)-5-methoxybenzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 468),-   2-[4-{2-(4-chlorophenyl)-5-(N-acetyl-N-isopropylamino)-benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 469),-   {[2-{4-[2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzoimidazol-5-yl]carbonyl-β-D-glucuronic    acid (Example 470),-   methyl    2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexyl-1H-indole-5-carboxylate    (Example 501),-   2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexyl-1H-indole-5-carboxylic    acid (Example 502),-   2-(4-benzyloxyphenyl)-1-cyclopentyl-1H-indole-5-carboxylic acid    (Example 503),-   ethyl    2-(4-benzyloxyphenyl)-3-cyclohexylimidazo[1,2-a]pyridine-7-carboxylate    (Example 601),-   2-(4-benzyloxyphenyl)-3-cyclohexylimidazo[1,2-a]pyridine-7-carboxylic    acid (Example 602),-   2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-3-cyclohexyl-3H-imidazo[4,5-b]pyridine-6-carboxylic    acid (Example 701),-   2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]phenyl}-3-cyclohexyl-3H-dimidazo[4,5-b]pyridine-6-carboxylic    acid hydrochloride (Example 702), and-   2-{4-[2-(4-chlorophenyl)-5-(pyrrolidin-1-ylcarbonyl)benzyloxy]-phenyl}-3-cyclohexyl-3H-imidazo[4,5-b]pyridine-6-carboxylic    acid hydrochloride (Example 703).-   (62) The fused ring compound of the formula [I] or a    pharmaceutically acceptable salt thereof, which is selected from the    group consisting of-   2-{4-[2-(4-chlorophenyl)-5-(4-oxopiperidinocarbonyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 328),-   2-{4-[2-(4-chlorophenyl)-5-hydroxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 329),-   2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 330),-   2-{4-[2-(4-chlorophenyl)-5-(N-isopropyl-N-methylcarbamoyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 331),-   2-{4-[2-(4-chlorophenyl)-5-(phenylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 332),-   2-{4-[2-(4-chlorophenyl)-5-(4-methoxypiperidinocarbonyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 333),-   2-{4-[2-(4-chlorophenyl)-5-(3-hydroxypropyloxy)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 334),-   2-{4-[2-(4-chlorophenyl)-5-(2-hydroxyethoxy)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 335),-   methyl    2-[4-(2-bromo-5-nitrobenzyloxy)-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate    (Example 336),-   methyl    2-[4-{2-(4-chlorophenyl)-5-nitrobenzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate    (Example 337),-   methyl    2-[4-{5-amino-2-(4-chlorophenyl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate    (Example 338),-   methyl    2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate    (Example 339),-   2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 340),-   2-{4-[2-(4-chlorophenyl)-5-(4-methylpiperidin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 341),-   2-{4-[5-acetyl-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 342),-   2-{4-[2-(4-chlorophenyl)-5-[{(4-hydroxypiperidin-1-ylcarbonyl)-methoxy}benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 343),-   2-{4-[2-(4-chlorophenyl)-5-(2-methoxyethoxy)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 344),-   2-{4-[2-(4-chlorophenyl)-5-{2-(2-methoxyethoxy)ethoxy}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 345),-   2-{4-[2-(4-chlorophenyl)-5-(isobutylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 346),-   2-{4-[2-(4-chlorophenyl)-5-(2-methylthiazol-4-yl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 347),-   2-{4-[2-(4-chlorophenyl)-5-(3,4-dihydroxypiperidin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 348),-   2-{4-[2-(4-chlorophenyl)-5-(3-methyl-1,2,4-oxadiazol-5-yl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 349),-   2-{4-[2-(4-chlorophenyl)-4-(isopropylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 350),-   2-{4-[2-(4-chlorophenyl)-4-(piperidinocarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 351),-   2-{4-[2-(4-chlorophenyl)-5-{(1-hydroxy-2-methylpropan-2-yl)carbamoyl}benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 352),-   2-{4-[2-(4-chlorophenyl)-5-(4,4-dimethyl-2-oxazolin-2-yl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid dihydrochloride (Example 353),-   2-{4-[2-(4-chlorophenyl)-4-(4-hydroxypiperidin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 354),-   2-{4-[2-(4-chlorophenyl)-4-{(2-hydroxyethyl)carbamoyl}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 355),-   2-{4-[2-(4-chlorophenyl)-4-{(4-pyridylmethyl)carbamoyl}-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 356),-   2-{4-[2-(4-chlorophenyl)-4-(dimethylcarbamoyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 357),-   2-{4-[5-(2-aminothiazol-4-yl)-2-(4-chlorophenyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid dihydrochloride (Example 358),-   2-{4-[2-(4-chlorophenyl)-5-(4-hydroxypiperidin-1-ylsulfonyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 359),-   2-{4-[5-(dimethylcarbamoyl)-2-(4-fluorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 360),-   2-{4-[5-(dimethylcarbamoyl)-2-(3-fluorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 361),-   2-{4-[2-(5-chlorothiophen-2-yl)-5-(dimethylcarbamoyl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 362),-   2-{4-[2-bromo-5-(5-methyloxazol-2-yl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 363),-   2-{4-[2-bromo-5-(5-methylthiazol-2-yl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 364),-   2-{4-[2-(4-chlorophenyl)-5-(5-methyloxazol-2-yl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 365),-   2-{4-[2-(4-chlorophenyl)-5-(5-methylthiazol-2-yl)benzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 366),-   2-{4-[2-(4-chlorophenyl)-5-tetrazol-5-ylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 367),-   2-{4-[5-chloro-2-(4-cyanophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 368),-   2-{4-[5-chloro-2-(4-tetrazol-5-ylphenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 369),-   2-{4-[2-(4-chlorophenyl)-5-{2-(4-hydroxypiperidin-1-yl)ethoxy}benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 370),-   2-{4-[2-(4-chlorophenyl)-5-(2-oxopiperidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 371),-   2-{4-[3-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 372),-   2-{4-[2-(4-chlorophenyl)-5-(N-hydroxyamidino)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid dihydrochloride (Example 373),-   2-{4-[2-(4-chlorophenyl)-5-(2,5-dihydro-5-oxo-4H-1,2,4-oxadiazol-3-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 374),-   2-{4-[2-(4-chlorophenyl)-5-(2-oxo-3H-1,2,3,5-oxathiadiazol-4-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 375),-   2-{4-[2-(4-chlorophenyl)-5-(2,5-dihydro-5-oxo-4H-1,2,4-thiadiazol-3-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 376),-   2-{4-[2-(4-chlorophenyl)-5-(cyclopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 377),-   2-{4-[2-(4-chlorophenyl)-5-(cyclobutylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 378),-   2-{4-[2-(4-chlorophenyl)-5-(tert-butylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 379),-   2-{4-[2-(4-chlorophenyl)-5-(isobutylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 380),-   2-{4-[2-(4-chlorophenyl)-5-{(1-hydroxypropan-2-yl)carbamoyl}-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 381),-   2-{4-[2-(4-chlorophenyl)-5-(methoxycarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 382),-   2-{4-[2-(4-chlorophenyl)-5-{(2,3-dihydroxypropyl)carbamoyl}-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 383),-   2-{4-[2-(4-chlorophenyl)-5-(N-ethyl-N-methylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 384),-   2-{4-[2-(4-chlorophenyl)-5-(N-methyl-N-propylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 385),-   2-{4-[2-(4-chlorophenyl)-5-(N-isopropyl-N-methylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 386),-   2-{4-[2-(4-chlorophenyl)-5-(2,6-dimethylpiperidin-1-ylcarbonyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 387),-   2-{4-[5-(butylcarbamoyl)-2-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 388),-   2-{4-[2-(4-chlorophenyl)-5-(propylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 389),-   2-{4-[2-(4-chlorophenyl)-5-(ethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 390),-   2-{4-[2-(4-chlorophenyl)-5-{(dimethylcarbamoyl)amino}benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 391),-   2-{4-[2-(4-chlorophenyl)-5-{(morpholinocarbonyl)amino}benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 392),-   2-{4-[2-(4-chlorophenyl)-5-ureidobenzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 393),-   2-{4-[2-(4-chlorophenyl)-5-{(ethylcarbamoyl)amino}benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 394),-   2-{4-[2-(4-chlorophenyl)-5-[(isopropylcarbamoyl)amino}benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 395),-   2-{4-[2-(3,4-difluorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 396),-   2-{4-[2-(2,4-difluorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 397),-   2-{4-[2-(3,5-dichlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 398),-   2-{4-[2-(3-chloro-4-fluorophenyl)-5-(isopropylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 399),-   2-{4-[2-(3,4-dichlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 400),-   2-{4-[2-(4-chloro-2-fluorophenyl)-5-(isopropylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 401),-   2-{4-[2-(4-chloro-2-fluorophenyl)-5-(pyrrolidin-1-ylcarbonyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 402),-   2-{4-[2-(4-chloro-3-fluorophenyl)-5-(pyrrolidin-1-ylcarbonyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 403),-   2-{4-[2-(4-chloro-3-fluorophenyl)-5-(isopropylcarbamoyl)-benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 404),-   2-{4-[2-{4-(methylthio)    phenyl}-5-(2-oxopyrrolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 405),-   2-{4-[2-{4-(methylthio)    phenyl}-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 406),-   2-{4-[4-chloro-2-(4-chlorophenyl)-5-(1,1-dioxoisothiazolidin-2-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 407),-   2-{4-[4-chloro-2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 408),-   2-{4-[2-(4-chlorophenyl)-5-(isopropylaminosulfonyl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 409),-   2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclopentylbenzimidazole-5-carboxylic    acid hydrochloride (Example 410),-   2-{4-[2-(4-chlorophenyl)-5-(4-hydroxypiperidin-1-ylcarbonyl)-benzyloxy]-2-fluorophenyl}-1-cyclopentylbenzimidazole-5-carboxylic    acid hydrochloride (Example 411),-   2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclopentylbenzimidazole-5-carboxylic    acid hydrochloride (Example 412),-   2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic    acid hydrochloride (Example 413),-   2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic    acid hydrochloride (Example 414),-   2-{4-[2-(4-chlorophenyl)-5-(4-hydroxypiperidin-1-ylcarbonyl)benzyloxy]phenyl}-1-cyclopentylbenzimidazole-5-carboxylic    acid hydrochloride (Example 415),-   2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]phenyl}-1-(tetrahydrothiopyran-4-yl)benzimidazole-5-carboxylic    acid hydrochloride (Example 416),-   2-{4-[2-(4-chlorophenyl)-5-(pyrrolidin-1-ylcarbonyl)benzyloxy]-phenyl}-1-(tetrahydrothiopyran-4-yl)benzimidazole-5-carboxylic    acid hydrochloride (Example 417),-   2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-(tetrahydrothiopyran-4-yl)benzimidazole-5-carboxylic    acid hydrochloride (Example 418),-   2-{4-[2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-(tetrahydrothiopyran-4-yl)benzimidazole-5-carboxylic    acid hydrochloride (Example 419),-   2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-piperidinobenzimidazole-5-carboxylic    acid hydrochloride (Example 420),-   2-{4-[2-(4-chlorophenyl)-5-(pyrrolidin-1-ylcarbonyl)benzyloxy]-2-fluorophenyl}-1-piperidinobenzimidazole-5-carboxylic    acid (Example 421),-   2-{4-[2-(4-chlorophenyl)-5-(2-imidazolin-2-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid dihydrochloride (Example 422),-   2-{4-[2-(4-chlorophenyl)-5-(2-oxooxazolidin-3-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 423),-   2-{4-[2-(4-chlorophenyl)-5-(2-oxoimidazolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 424),-   2-{4-[2-(4-chlorophenyl)-5-(2-oxazolin-2-ylamino)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid dihydrochloride (Example 425),-   2-{4-[{2-[{(dimethylcarbamoyl)methoxy}methyl]-4-(4-fluorophenyl)thiazol-5-yl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 426),-   2-{4-[{4-(4-fluorophenyl)-2-(4-hydroxypiperidin-1-ylmethyl)thiazol-5-yl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid dihydrochloride (Example 427),-   2-{4-[{4-(4-fluorophenyl)-2-[(carbamoylmethoxy)methyl]thiazol-5-yl}methoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 428),-   2-{4-[{4-(4-fluorophenyl)-2-(methylcarbamoyl)thiazol-5-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 429),-   2-{4-[{4-(4-fluorophenyl)-2-{(2-hydroxyethyl)carbamoyl}thiazol-5-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 430),-   2-{4-[{2-(4-fluorophenyl)-5-(dimethylcarbamoyl)thiophen-3-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 431),-   2-{4-[{2-(4-fluorophenyl)-5-(isopropylcarbamoyl)thiophen-3-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 432),-   2-{4-[{2-(4-fluorophenyl)-5-(4-hydroxypiperidin-1-ylcarbonyl)thiophen-3-yl}methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 433),-   2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexyl-5-tetrazol-5-ylbenzimidazole    (Example 434),-   2-{4-[2-(4-carboxyphenyl)-5-chlorobenzyloxy]-2-fluorophenyl}-1-cyclohexyl-5-tetrazol-5-ylbenzimidazole    hydrochloride (Example 435),-   2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]-2-fluorophenyl}-1-cyclohexyl-5-(2,5-dihydro-5-oxo-4H-1,2,4-oxadiazol-3-yl)benzimidazole    hydrochloride (Example 436),-   2-{4-[5-carboxy-2-(4-chlorophenyl)benzyloxy]-2-fluorophenyl}-5-cyano-1-cyclohexylbenzimidazole    (Example 437),-   2-{4-[2-(4-chlorophenyl)-5-(dimethylcarbamoyl)benzyloxy]-2-fluorophenyl}-5-cyano-1-cyclohexylbenzimidazole    (Example 438),-   2-{4-[{N-(4-dimethylcarbamoyl)-N-(4-fluorophenyl)amino}-methyl]phenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 439),-   2-{5-[bis(3-fluorophenyl)methyl]-2-fluoro-4-hydroxyphenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 440),-   2-{3-[bis(3-fluorophenyl)methyl]-2-fluoro-4-hydroxyphenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 441),-   2-{4-[(3-dimethylcarbamoylphenyl)(4-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 442),-   2-{4-[{3-(4-hydroxypiperidyl-1-ylcarbonyl)phenyl}(4-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 443),-   1-{[2-{4-([4-(4-fluorophenyl)-2-methylthiazol-5-yl]methoxy)phenyl}-1-cyclohexylbenzimidazol-5-yl]carbonyl}-β-D-glucuronic    acid (Example 444),-   {[2-{4-[bis(3-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazol-5-yl]carbonyl}-β-D-glucuronic    acid (Example 445),-   2-{4-[2-(4-chlorophenyl)-5-(1,1-dioxoisothiazolidin-2-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 446),-   3-{[4-(5-aminosulfonyl-1-cyclohexylbenzimidazol-2-yl)-3-fluorophenoxy]methyl}-4-(4-chlorophenyl)-N-isopropylbenzamide    (Example 447),-   2-[4-{2-(4-chlorophenyl)-6-(isopropylaminocarbonyl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 448),-   2-[4-{2-(4-chlorophenyl)-4-fluoro-5-(1,1-dioxoisothiazolidin-2-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 449),-   2-[4-{2-(4-chlorophenyl)-5-(isopropylaminocarbonyl)benzyloxy}-2-fluorophenyl]-1-cyclohexyl-4-methoxybenzimidazole-5-carboxylic    acid hydrochloride (Example 450),-   2-[4-{2-(4-chlorophenyl)-5-(N-isopropylcarbonyl-N-methylamino)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 451),-   2-[4-{2-(4-chlorophenyl)-5-(isopropylcarbonylamino)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 452),-   2-[3-{[4-(4-fluorophenyl)-2-methylthiazol-5-yl]methyl}-4-hydroxyphenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 453),-   2-[4-{2-(4-chlorophenyl)-4-fluoro-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 454),-   2-[4-{2-(4-chlorophenyl)-5-(methylsulfonylamino)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 455),-   2-[4-{2-(4-chlorophenyl)-5-[N-methyl-N-(methylsulfonyl)amino]benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 456),-   2-[4-{[3-(4-chlorophenyl)-6-(2-oxopyrrolidin-1-yl)pyridin-2-yl]methyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 457),-   2-[4-{2-(4-chlorophenyl)-5-(acetylamino)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 458),-   2-[4-{2-(4-chlorophenyl)-5-(N-acetyl-N-ethylamino)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 459),-   2-[4-{2-(4-chlorophenyl)-5-(N-acetyl-N-propylamino)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 460),-   2-[4-{2-(4-chlorophenyl)-5-[N-ethyl-N-(methylsulfonyl)amino]-benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 461),-   2-[4-{2-(4-chlorophenyl)-5-[N-(methylsulfonyl)-N-propylamino]benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 462),-   2-[4-{2-(4-chlorophenyl)-5-(N-acetyl-N-methylamino)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 463),-   2-[4-{2-(4-chlorophenyl)-5-[N-(ethylsulfonyl)-N-methylamino]-benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 464),-   2-[4-{2-(4-chlorophenyl)-5-[N-ethyl-N-(ethylsulfonyl)amino]-benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 465),-   2-[4-{2-(4-chlorophenyl)-5-[N-(ethylcarbonyl)-N-methylamino]-benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 466),-   2-[4-{2-(4-chlorophenyl)-5-[N-ethyl-N-(ethylcarbonyl)amino]-benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 467),-   2-[4-{2-(4-chlorophenyl)-5-methoxybenzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid (Example 468),-   2-[4-{2-(4-chlorophenyl)-5-(N-acetyl-N-isopropylamino)-benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylic    acid hydrochloride (Example 469),-   {[2-{4-[2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzoimidazol-5-yl]carbonyl-β-D-glucuronic    acid (Example 470),-   2-{4-[2-(4-chlorophenyl)-5-(isopropylcarbamoyl)benzyloxy]phenyl}-3-cyclohexyl-3H-dimidazo[4,5-b]pyridine-6-carboxylic    acid hydrochloride (Example 702), and-   2-{4-[2-(4-chlorophenyl)-5-(pyrrolidin-1-ylcarbonyl)benzyloxy]-phenyl}-3-cyclohexyl-3H-imidazo[4,5-b]pyridine-6-carboxylic    acid hydrochloride (Example 703).-   (63) A pharmaceutical composition comprising a fused ring compound    of any of (29) to (62) above, or a pharmaceutically acceptable salt    thereof, and a pharmaceutically acceptable carrier.-   (64) A hepatitis C virus polymerase inhibitor comprising a fused    ring compound of any of (1) to (28) and (29) to (62) above, or a    pharmaceutically acceptable salt thereof, and a pharmaceutically    acceptable carrier.-   (65) An anti-hepatitis C virus agent comprising a fused ring    compound of any of (1) to (28) and (29) to (62) above, or a    pharmaceutically acceptable salt thereof, and a pharmaceutically    acceptable carrier.-   (66) A therapeutic agent for hepatitis C comprising a fused ring    compound of any of (29) to (62) above, or a pharmaceutically    acceptable salt thereof, and a pharmaceutically acceptable carrier.-   (67) An anti-hepatitis C virus agent comprising (a) the    anti-hepatitis C virus agent of (65) above and (b) at least one    agent selected from the group consisting of a different antiviral    agent, an antiinflammatory agent and an immunostimulant.-   (68) An anti-hepatitis C virus agent comprising (a) the    anti-hepatitis C virus agent of (65) above and (b) interferon.-   (69) A therapeutic agent for hepatitis C comprising (a) the    hepatitis C virus polymerase inhibitor of (64) above and (b) at    least one agent selected from the group consisting of a different    antiviral agent, an antiinflammatory agent and an immunostimulant.-   (70) A therapeutic agent for hepatitis C comprising (a) the    hepatitis C virus polymerase inhibitor of (64) above and (b)    interferon.-   (71) A benzimidazole compound of the folllowing formula [III]    wherein R^(a36) is hydrogen atom or carboxyl-protecting group,    R^(a37) is cyclopentyl or cyclohexyl, and R^(a38) is hydrogen atom    or fluorine atom, or a salt thereof.-   (72) A thiazole compound selected from the group consisting of    4-(4-fluorophenyl)-5-hydroxymethyl-2-methylthiazole and    4-(4-fluorophenyl)-5-chloromethyl-2-methylthiazole, or a    pharmaceutically acceptable salt thereof.-   (73) A biphenyl compound selected from the group consisting of    1-(4′-chloro-2-hydroxymethyl-biphenyl-4-yl)-2-pyrrolidinone and    1-(4′-chloro-2-chloromethyl-biphenyl-4-yl)-2-pyrrolidinone, or a    pharmaceutically acceptable salt thereof.-   (74) A pharmaceutical composition comprising (a) a fused ring    compound of the formula [I] of (1) above or a pharmaceutically    acceptable salt thereof and (b) at least one agent selected from the    group consisting of an antiviral agent other than the compound    of (1) above, an antiinflammatory agent and an immunostimulant.-   (75) A pharmaceutical composition comprising (a) a fused ring    compound of the formula [I] of (1) above or a pharmaceutically    acceptable salt thereof and (b) interferon.-   (76) A method for treating hepatitis C, which comprises    administering an effective amount of a fused ring compound of the    formula [I] of (1) above or a pharmaceutically acceptable salt    thereof.-   (77) The method of (76) above, further comprising administering an    effective amount of at least one agent selected from the group    consisting of an antiviral agent other than the compound of claim 1,    an antiinflammatory agent and an immunostimulant.-   (78) The method of (76) above, further comprising administering an    effective amount of interferon.-   (79) A method for inhibiting hepatitis C virus polymerase, which    comprises administering an effective amount of a fused ring compound    of the formula [I] of (1) above or a pharmaceutically acceptable    salt thereof.-   (80) The method of (79) above, further comprising administering an    effective amount of at least one agent selected from the group    consisting of an antiviral agent other than the compound of (1)    above, an antiinflammatory agent and an immunostimulant.-   (81) The method of (79) above, further comprising administering an    effective amount of interferon.-   (82) Use of a fused ring compound of the formula [I] of (1) above or    a pharmaceutically acceptable salt thereof for the production of a    pharmaceutical agent for treating hepatitis C.-   (83) Use of a fused ring compound of the formula [I] of (1) above or    a pharmaceutically acceptable salt thereof for the production of a    hepatitis C virus polymerase inhibitor.-   (84) A pharmaceutical composition for the treatment of hepatitis C,    which comprises a fused ring compound of the formula [I] of (1)    above or a pharmaceutically acceptable salt thereof, and a    pharmaceutically acceptable carrier.-   (85) A pharmaceutical composition for inhibiting hepatitis C virus    polymerase, which comprises a fused ring compound of the formula [I]    of (1) above or a pharmaceutically acceptable salt thereof, and a    pharmaceutically acceptable carrier.-   (86) A commercial package comprising a pharmaceutical composition    of (84) above and a written matter associated therewith, the written    matter stating that the pharmaceutical composition can or should be    used for treating hepatitis C.-   (87) A commercial package comprising a pharmaceutical composition    of (85) above and a written matter associated therewith, the written    matter stating that the pharmaceutical composition can or should be    used for inhibiting hepatitis C virus polymerase.-   (88) 1-Cyclohexyl-2-(3-furanyl)-1H-benzimidazole-5-carboxylic acid    (Example 471).

DETAILED DESCRIPTION OF THE INVENTION

The definitions of respective substituents and moieties used in thepresent specification are as follows.

The halogen atom is a fluorine atom, chlorine atom, bromine atom oriodine atom, preferably fluorine atom, chlorine atom or bromine atom.

Particularly preferably, the halogen atom is fluorine atom at R⁵, R⁵′,R⁶, R⁶′, group A and group C, and fluorine atom or chlorine atom at X,Z, Z′, group B and group D.

The C₁₋₆ alkyl is straight chain or branched chain alkyl having 1 to 6carbon atoms, and is exemplified by methyl, ethyl, propyl, isopropyl,butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, tert-pentyl,hexyl and the like.

Preferably, it is straight chain or branched chain alkyl having 1 to 4carbon atoms, and is particularly preferably methyl at R^(a7), R^(a8),R^(a9), R^(a15), R^(a16), R^(a17), R^(a33), R^(a35), R^(b6) and R^(b7)and methyl or tert-butyl at R^(b1), R^(b2), group B and group C, andmethyl, ethyl, propyl or isopropyl at R^(a29).

The halogenated C₁₋₆ alkyl is the above-defined C₁₋₆ alkyl except thatit is substituted by the above-defined halogen atom. Preferably, it ishalogenated alkyl wherein the alkyl moiety thereof is straight chain orbranched chain alkyl having 1 to 4 carbon atoms. Examples thereofinclude fluoromethyl, difluoromethyl, trifluoromethyl, bromomethyl,chloromethyl, 1,2-dichloromethyl, 2,2-dichloromethyl,2,2,2-trifluoroethyl and the like.

The halogenated C₁₋₆ alkyl is particularly preferably trifluoromethyl atgroup B.

The C₁₋₆ alkylene is straight chain alkylene having 1 to 6 carbon atoms,and is exemplified by methylene, ethylene, trimethylene, tetramethylene,pentamethylene or hexamethylene.

The C₁₋₆ alkylene is preferably methylene or ethylene at Y.

The C₂₋₆ alkenylene is straight chain alkenylene having 2 to 6 carbonatoms, and is exemplified by vinylene, propenylene, 1-butenylene,1,3-butadienylene and the like.

The C₂₋₆ alkenylene is preferably vinylene at Y.

The C₁₋₆ alkoxy is alkyloxy wherein the alkyl moiety thereof is theabove-defined C₁₋₆ alkyl. Preferably, it is alkoxy wherein the alkylmoiety thereof is straight chain or branched chain alkyl having 1 to 4carbon atoms. Examples thereof include methoxy, ethoxy, propoxy,isopropyloxy, butoxy, isobutyloxy, tert-butyloxy, pentyloxy, hexyloxyand the like.

The C₁₋₆ alkoxy is particularly preferably methoxy at R^(a2), R^(a3),R^(a27), R^(a28), R^(a33), group A and group C.

The C₁₋₆ alkoxy C₁₋₆ alkoxy is that wherein C₁₋₆ alkoxy in the abovedefinition is substituted by C₁₋₆ alkoxy defined above and is preferablythat wherein the alkyl moiety thereof is straight chain or branchedchain alkyl having 1 to 4 carbon atoms. Specific examples includemethoxymethyl, ethoxymethyl, methoxyethoxy, methoxypropoxy,isopropyloxyethoxy and the like.

The group A is particularly preferably methoxyethoxy.

The C₁₋₆ alkanoyl is alkylcarbonyl wherein the alkyl moiety thereof isthe above-defined C₁₋₆ alkyl. Preferably, it is alkanoyl wherein thealkyl moiety thereof is straight chain or branched chain alkyl having 1to 4 carbon atoms. Examples thereof include acetyl, propionyl, butyryl,isobutyryl, pivaloyl and the like.

The C₁₋₆ alkanoyl is particularly preferably acetyl at R¹, R², R³, R⁴,R^(a5), R^(a29), R^(b7) and group B.

The C₁₋₆ alkoxycarbonyl is alkyloxycarbonyl wherein the alkoxy moietythereof is the above-defined C₁₋₆ alkoxy. Preferably, it isalkoxycarbonyl wherein the alkyl moiety thereof is straight chain orbranched chain alkyl having 1 to 4 carbon atoms. Examples thereofinclude methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,isopropyloxycarbonyl, butoxycarbonyl, isobutyloxycarbonyl,tert-butyloxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl and the like.

The C₁₋₆ alkoxycarbonyl is particularly preferably methoxycarbonyl orethoxycarbonyl at R^(a10) and group A.

The C₁₋₆ alkylamino is alkylamino or dialkylamino wherein the alkylmoiety thereof is the above-defined C₁₋₆ alkyl. Preferably, it isalkylamino or dialkylamino wherein the alkyl moiety thereof is straightchain or branched chain alkyl having 1 to 4 carbon atoms. Examplesthereof include methylamino, ethylamino, propylamino, isopropylamino,butylamino, isobutylamino, tert-butylamino, pentylamino, hexylamino,dimethylamino, diethylamino, methylethylamino,N-isopropyl-N-isobutylamino and the like.

The C₁₋₆ alkylamino is particularly preferably methylamino at R^(a7),and particularly preferably dimethylamino at R^(a21) and group A, andparticularly preferably dimethylamino, ethylamino or isopropylamino atR^(a24).

The C₁₋₆ alkanoylamino is alkylcarbonylamino wherein the alkanoyl moietythereof is the above-defined C₁₋₆ alkanoyl. Preferably, it isalkylcarbonylamino wherein the alkyl moiety thereof is straight chain orbranched chain alkyl having 1 to 4 carbon atoms. Examples thereofinclude acetylamino, propionylamino, butyrylamino, isobutyrylamino,pivaloylamino and the like.

The C₁₋₆ alkanoylamino is particularly preferably acetylamino at X andR^(a10).

The C₁₋₆ alkylsulfonyl is alkylsulfonyl wherein the alkyl moiety thereofis the above-defined C₁₋₆ alkyl. Preferably, it is alkylsulfonyl whereinthe alkyl moiety thereof is straight chain or branched chain alkylhaving 1 to 4 carbon atoms. Examples thereof include methylsulfonyl,ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl,isobutylsulfonyl, tert-butylsulfonyl, pentylsulfonyl, hexylsulfonyl andthe like.

The C₁₋₆ alkylsulfonyl is particularly preferably methylsulfonyl at Xand R^(a5).

The C₆₋₁₄ aryl is aromatic hydrocarbon having 6 to 14 carbon atoms.Examples thereof include phenyl, naphthyl, anthryl, indenyl, azulenyl,fluorenyl, phenanthryl and the like.

The C₆₋₁₄ aryl is preferably phenyl or naphthyl, particularly preferablyphenyl at the ring A, ring A′, ring B and ring B′.

The C₃₋₈ cycloalkyl is saturated cycloalkyl having 3 to 8, preferably 5to 7, carbon atoms. Examples thereof include cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl.

The C₃₋₈ cycloalkyl is particularly preferably cyclohexyl at the ring A,ring A′, ring B and ring B′.

The C₃₋₈ cycloalkenyl is cycloalkenyl having 3 to 8, preferably 5 to 7,carbon atoms and has at least 1, preferably 1 or 2, double bond(s).Examples thereof include cyclopropenyl, cyclobutenyl, cyclopentenyl,cyclopentadienyl, cyclohexenyl, 2,4-cyclohexadien-1-yl,2,5-cyclohexadien-1-yl, cycloheptenyl and cyclooctenyl and the like, butdo not include aryl (e.g., phenyl) or completely saturated cycloalkyl.

The C₃₋₈ cycloalkenyl is preferably cyclohexenyl at the ring A and ringA′.

The heterocyclic group has, as an atom constituting the ring, 1 to 4heteroatom(s) selected from an oxygen atom, a nitrogen atom and a sulfuratom, besides a carbon atom, and includes saturated ring and unsaturatedring, monocyclic ring and fused ring having the number of ring atomconstituting the ring of 3 to 14.

The heterocyclic group as a monocyclic ring includes, for example,pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl, pyrrolyl,pyrazolyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, thienyl, furyl,oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolinyl,pyrrolidinyl, imidazolidinyl, piperidyl, piperazinyl, morpholinyl,thiomorpholinyl, tetrahydropyranyl and the like.

The heterocyclic group includes the groups of the following formulas.

wherein E¹ is an oxygen atom, a sulfur atom or N(—R^(a35)), E² is anoxygen atom, CH₂ or N(—R^(a35)), E³ is an oxygen atom or a sulfur atom,wherein R^(a35) is independently hydrogen atom or C₁₋₆ alkyl, f is aninteger of 1 to 3, and h and h′ are the same or different and each is aninteger of 1 to 3.

Specific examples of the heterocyclic group include

and the like.

Examples of the heterocyclic group as a fused ring include quinolyl,isoquinolyl, quinazolinyl, quinoxalyl, phthalazinyl, cinnolinyl,naphthyridinyl, 5,6,7,8-tetrahydroquinolyl, indolyl, benzimidazolyl,2,3-dihydrobenzimidazolyl, 2,3-dihydro-2-oxobenzimidazolyl, indolinyl,benzofuranyl, benzothienyl, benzoxazolyl, benzothiazolyl and the like.

Preferably, it is a heterocyclic group which is a 5-membered or a6-membered monocyclic group. Examples thereof include pyridyl,pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl, pyrrolyl,pyrazolyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, thienyl, furyl,oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, thiadiazolyl,pyrrolidinyl, piperidyl, piperazinyl

and the like.

At R¹, R², R³, R⁴, Z and group D, tetrazolyl and5-oxo-Δ²-1,2,4-oxadiazolin-3-yl are particularly preferable.

The heterocyclic group is preferably pyridyl, pyrazinyl, pyrimidinyl orpyridazinyl which is an aromatic group, and particularly preferablypyridyl at the ring A and ring A′.

The heterocyclic group is particularly preferably pyridyl, pyrazinyl,pyrimidinyl, pyridazinyl, 1,3,5-triazinyl, pyrrolyl, pyrazolyl,imidazolyl, 1,2,4-triazolyl, tetrazolyl, thienyl, furyl, oxazolyl,isoxazolyl, thiazolyl, isothiazolyl or thiadiazolyl, which is anaromatic group, at the ring B and ring B′. More preferably it is pyridylor thiazolyl, most preferably thiazolyl.

The C₆₋₁₄ aryl C₁₋₆ alkyl is arylalkyl wherein the alkyl moiety thereofis the above-defined C₁₋₆ alkyl and the aryl moiety is the above-definedC₆₋₁₄ aryl. Preferably, it is arylalkyl wherein the alkyl moiety thereofis straight chain alkyl having 1 to 4 carbon atoms and the aryl moietyis phenyl. Examples thereof include benzyl, phenethyl, 3-phenylpropyl,2-phenylpropyl, 4-phenylbutyl and the like.

The C₆₋₁₄ aryl C₁₋₆ alkyl is particularly preferably benzyl at R^(a8)and R^(b6).

The glucuronic acid residue is glucuronic acid less any hydroxyl group,preferably β-D-glucuronic acid substituted at 1-position.

The C₆₋₁₄ aryl C₁₋₆ alkyloxycarbonyl is arylalkyloxycarbonyl wherein theC₆₋₁₄ aryl C₁₋₆ alkyl moiety thereof is the above-defined C₆₋₁₄ arylC₁₋₆ alkyl. Preferably, it is arylalkyloxycarbonyl wherein the alkylmoiety thereof is straight chain alkyl having 1 to 4 carbon atoms andthe aryl moiety is phenyl. Examples thereof include benzyloxycarbonyl,phenethyloxycarbonyl, 3-phenylpropyloxycarbonyl,2-phenylpropyloxycarbonyl, 4-phenylbutyloxycarbonyl and the like.

The C₆₋₁₄ aryl C₁₋₆ alkyloxycarbonyl is particularly preferablybenzyloxycarbonyl at R^(b7).

The optionally substituted C₁₋₆ alkyl is the above-defined C₁₋₆ alkyl,preferably that wherein straight chain or branched chain alkyl having 1to 4 carbon atoms is optionally substituted with 1 to 3 substituent(s),and includes unsubstituted alkyl. The substituent(s) is(are) selectedfrom the above-defined halogen atom, hydroxyl group, carboxyl, amino,the above-defined C₁₋₆ alkoxy, the above-defined C₁₋₆ alkoxy C₁₋₆alkoxy, the above-defined C₁₋₆ alkoxycarbonyl and the above-defined C₁₋₆alkylamino. Examples of optionally substituted C₁₋₆ alkyl includemethyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl,tert-butyl, pentyl, isopentyl, tert-pentyl, neopentyl, 1-ethylpropyl,hexyl, trifluoromethyl, hydroxymethyl, 2-hydroxyethyl, 3-hydroxypropyl,4-hydroxybutyl, 1-hydroxy-1-methylethyl, 1-hydroxypropan-2-yl,1,3-dihydroxypropan-2-yl, 1-hydroxy-2-methylpropan-2-yl, carboxylmethyl,2-carboxylethyl, methoxymethyl, methoxyethyl, methoxyethoxyethyl,ethoxycarbonylmethyl, 2-ethoxycarbonylethyl, 2-dimethylaminoethyl andthe like.

Preferably, the optionally substituted C₁₋₆ alkyl is methyl,1-hydroxy-1-methylethyl, carboxylmethyl or 2-dimethylaminoethyl at R¹,R², R² and R³, methyl or trifluoromethyl at R⁵, R⁵′, R⁶ and R⁶′, methylat R⁷, R⁸, R^(a31) and R^(b5), methyl, ethyl or isopropyl at R^(a24),methyl or isopropyl at R^(a18), methyl or ethyl at R^(a1), R^(a19) andR^(a25), methyl, carboxylmethyl or 2-dimethylaminoethyl at R^(a2) andR^(a3), methyl or carboxylmethyl at R^(a6), methyl, ethyl, isopropyl,butyl or trifluoromethyl at X, methyl, ethyl, isopropyl, butyl,isobutyl, tert-butyl, isopentyl, neopentyl, 1-ethylpropyl orcarboxylmethyl at R^(a10), methyl, ethyl, propyl, isopropyl, butyl,isobutyl, trifluoromethyl, 2-hydroxyethyl or carboxylmethyl at R^(a11),methyl or 4-hydroxybutyl at R^(a12), methyl, ethyl, isopropyl, butyl,2-hydroxyethyl, 4-hydroxybutyl, ethoxycarbonylmethyl,2-(ethoxycarbonyl)ethyl or 2-dimethylaminoethyl at R^(a13), methyl,propyl, butyl, isopentyl, trifluoromethyl, hydroxymethyl,2-hydroxyethyl, 3-hydroxypropyl, methoxyethyl, methoxyethoxyethyl orcarboxymethyl at R^(a20), methyl or ethyl at R^(a22) and R^(a23), methylisopropyl or tert-butyl at R^(a26), methyl, ethyl, propyl, isopropyl,butyl, tert-butyl, isobutyl, 2-hydroxyethyl, 1-hydroxypropan-2-yl,1-hydroxy-2-methylpropan-2-yl or carboxylmethyl at R^(a27) and R^(a28),and methyl, ethyl, propyl, isopropyl, tert-butyl, trifluoromethyl,hydroxymethyl, 2-hydroxyethyl, 2-carboxylethyl, methoxymethyl orethoxycarbonylmethyl at Z, Z′ and group D.

It is particularly preferably, trifluoromethyl at R⁵, R⁵′, R⁶ and R⁶′,methyl or tert-butyl at R^(a26), methyl, tert-butyl, trifluoromethyl orhydroxymethyl at Z, Z′ and group D, and methyl at other substituents.

The optionally substituted C₂₋₆ alkenyl is that wherein straight chainor branched chain alkenyl having 2 to 6 carbon atoms is optionallysubstituted by 1 to 3 substituent(s), and includes unsubstitutedalkenyl. The substituent (s) is (are) selected from the above-definedhalogen atom, hydroxyl group, carboxyl, amino, the above-defined C₁₋₆alkoxy, the above-defined C₁₋₆ alkoxy C₁₋₆ alkoxy, the above-definedC₁₋₆ alkoxycarbonyl and the above-defined C₁₋₆ alkylamino. Examples ofoptionally substituted C₂₋₆ alkenyl include vinyl, allyl, 1-propenyl,isopropenyl, 1-butenyl, 2-butenyl, 1,3-butadienyl, 2-isopentenyl,3-isohexenyl, 4-methyl-3-pentenyl, 2-carboxylethenyl and the like.

The optionally substituted C₂₋₆ alkenyl is preferably 2-carboxylethenylat X, and preferably 2-isopentenyl, 3-isohexenyl or 4-methyl-3-pentenylat R^(a20).

The optionally substituted C₂₋₆ alkynyl is that wherein straight chainor branched chain alkynyl having 2 to 6 carbon atoms is optionallysubstituted by 1 to 3 substituent(s), and includes unsubstitutedalkynyl. The substituent(s) is(are) selected from the above-definedhalogen atom, hydroxyl group, carboxyl, amino, the above-defined C₁₋₆alkoxy, the above-defined C₁₋₆ alkoxycarbonyl and the above-defined C₁₋₆alkylamino. Examples thereof include ethynyl, 1-propynyl, 2-propynyl,3-butynyl and the like.

The optionally substituted C₂₋₆ alkynyl is preferably 2-propynyl atR^(a20).

The C₆₋₁₄ aryl optionally substituted by 1 to 5 substituent(s) selectedfrom group B is that wherein the above-defined C₆₋₁₄ aryl is optionallysubstituted by 1 to 5 substituent(s), and includes unsubstituted aryl.The substituent(s) is(are) selected from the above-defined halogen atom,cyano, nitro, the above-defined C₁₋₆ alkyl, the above-definedhalogenated C₁₋₆ alkyl, the above-defined C₁₋₆ alkanoyl,—(CH₂)_(r)—COOR^(b1), —(CH₂)_(r)—CONR^(b1)R^(b2),—(CH₂)_(r)—NR^(b1)R^(b2), —(CH₂)_(r)—NR^(b1)—COR^(b2),—(CH₂)_(r)—NHSO₂R^(b1) —(CH₂)_(r)—OR^(b1), —(CH₂)_(r)—SR^(b1),—(CH₂)_(r)—SO₂R¹ and —(CH₂)_(r)—SO₂NR^(b1)R^(b2) (wherein R^(b1) andR^(b2) are each independently hydrogen atom or the above-defined C₁₋₆alkyl and r is 0 or an integer of 1 to 6).

Examples thereof include phenyl, naphthyl, anthryl, indenyl, azulenyl,fluorenyl, phenanthryl, 3-fluorophenyl, 4-fluorophenyl, 3-chlorophenyl,4-chlorophenyl, 2,4-dichlorophenyl, 3,5-dichlorophenyl,pentafluorophenyl, 4-methylphenyl, 4-tert-butylphenyl,2-trifluoromethylphenyl, 4-trifluoromethylphenyl, 4-nitrophenyl,4-cyanophenyl, 4-acetylphenyl, 4-carboxylphenyl, 4-carbamoylphenyl,4-aminophenyl, 4-dimethylaminophenyl, 4-acetylaminophenyl,4-(methylsulfonylamino)phenyl, 4-methoxyphenyl, 3,4,5-trimethoxyphenyl,4-methylthiophenyl, 4-methylsulfonylphenyl, 4-aminosulfonylphenyl,3-nitro-4-methoxyphenyl and 4-nitro-3-methoxyphenyl.

The aryl moiety is preferably phenyl, the group B here is preferably theabove-defined halogen atom, nitro, the above-defined C₁₋₆ alkyl, theabove-defined halogenated C₁₋₆ alkyl or —(CH₂)_(r)—OR^(b1). Examples ofgroup B include fluorine atom, chlorine atom, nitro, methyl, tert-butyl,trifluoromethyl and methoxy. Particularly preferably, it is fluorineatom or chlorine atom.

With regard to “C₆₋₁₄ aryl optionally substituted by 1 to 5substituent(s) selected from group B”, it is preferably phenyl,4-tert-butylphenyl, 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl,4-methoxyphenyl or 4-trifluoromethylphenyl at R^(a12), R^(a27) andR^(a28), phenyl at R^(a14), R^(a22), R^(a23), R^(a26) and R^(b5), phenylor 3 fluorophenyl at R^(a18), phenyl or 2,4-dichlorophenyl at R^(a20),phenyl, 4-chlorophenyl, 4-trifluoromethylphenyl, 3,5-dichlorophenyl,3-nitro-4-methoxyphenyl or 4-nitro-3-methoxyphenyl at R^(a24), andphenyl or 4-methylphenyl at R^(a25).

It is particularly preferably phenyl at other substituents.

The C₆₋₁₄ aryl optionally substituted by 1 to 5 substituent(s) selectedfrom group D is that wherein the above-defined C₆₋₁₄ aryl is optionallysubstituted by 1 to 5 substituent(s), and includes unsubstituted aryl.The substituent(s) is(are) selected from the above-mentioned group D(substituents shown under (a) to (q)).

Examples of group D here include fluorine atom, chlorine atom, bromineatom, nitro, cyano, methyl, ethyl, propyl, isopropyl, tert-butyl,trifluoromethyl, hydroxymethyl, 2-hydroxyethyl, methoxymethyl,2-carboxylethyl, methoxycarbonylmethyl, ethoxycarbonylmethyl, acetyl,carboxyl, methoxycarbonyl, ethoxycarbonyl, carbamoyl,methylaminocarbonyl, isopropylaminocarbonyl, dimethylaminocarbonyl,diethylaminocarbonyl, (2-hydroxyethyl)aminocarbonyl,(carboxylmethyl)aminocarbonyl, hydroxyl group, methoxy, ethoxy,propyloxy, isopropyloxy, isopentyloxy, 2-isopentenyloxy,3-isohexenyloxy, 4-methyl-3-pentenyloxy, 2-propynyloxy,hydroxymethyloxy, carboxylmethyloxy, (dimethylaminocarbonyl)methyloxy,amino, methylamino, dimethylamino, diethylamino, acetylamino,methylsulfonylamino, methylthio, methylsulfonyl, methylsulfinyl,aminosulfonyl, methylaminosulfonyl, dimethylaminosulfonyl andtetrazolyl.

Examples of C₆₋₁₄ aryl optionally substituted by 1 to 5 substituent(s)selected from group D include phenyl, naphthyl, anthryl, indenyl,azulenyl, fluorenyl, phenanthryl, 3-fluorophenyl, 4-fluorophenyl,3-chlorophenyl, 4-chlorophenyl, 2,4-dichlorophenyl, 3,5-dichlorophenyl,4-bromophenyl, 4-nitrophenyl, pentafluorophenyl, 4-methylphenyl,4-tert-butylphenyl, 2-trifluoromethylphenyl, 4-trifluoromethylphenyl,4-(hydroxymethyl)phenyl, 4-(methoxymethyl)phenyl,4-(2-carboxylethyl)phenyl, 3-carboxylphenyl, 4-carboxylphenyl,4-methoxyphenyl, 3,4,5-trimethoxyphenyl, 4-carbamoylphenyl,4-methylthiophenyl, 4-(dimethylaminocarbonyl)phenyl,4-methylsulfonylphenyl, 4-acetylaminophenyl, 4-cyanophenyl,4-acetylphenyl, 4-aminophenyl, 4-dimethylaminophenyl,4-(methylsulfonylamino)phenyl, 4-methylsulfinylphenyl,4-aminosulfonylphenyl and 3-nitro-4-methoxyphenyl,4-nitro-3-methoxyphenyl and 4-tetrazol-5-ylphenyl.

At Z and Z′, the aryl moiety is preferably phenyl.

The group D here is preferably the above-defined halogen atom, nitro,the above-defined optionally substituted C₁₋₆ alkyl,(CH₂)_(t)—COOR^(a19), —(CH₂)_(t)—CONR^(a27)R^(a28), —(CH₂)_(t)—OR^(a20),—(CH₂)_(t)—NR^(a29)CO—R^(a24), —(CH₂)_(t)—S(O)_(q)—R^(a25) or—(CH₂)_(t)—SO₂—NHR^(a26).

Particularly preferably, it is the above-defined halogen atom, theabove-defined optionally substituted C₁₋₆ alkyl, —(CH₂)_(t)—COOR^(a19)—,—(CH₂)_(t)—CONR^(a27)R^(a28), —(CH₂)_(t)—OR^(a20) or—(CH₂)_(t)—S(O)_(q)—R^(a25), which is specifically fluorine atom,chlorine atom, bromine atom, nitro, methyl, tert-butyl, carboxyl,trifluoromethyl, hydroxymethyl, methoxymethyl, 2-carboxylethyl, methoxy,carbamoyl, methylthio, dimethylaminocarbonyl, methylsulfonyl oracetylamino. More preferably, it is fluorine atom, chlorine atom,methyl, tert-butyl, carboxyl, methoxy, carbamoyl, methylthio,dimethylaminocarbonyl, methylsulfonyl or acetylamino, most preferablyfluorine atom or chlorine atom.

Examples of C₆₋₁₄ aryl optionally substituted by 1 to 5 substituent(s)selected from group D preferably include phenyl, 3-fluorophenyl,4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3,5-dichlorophenyl,4-bromophenyl, 4-nitrophenyl, 4-methylphenyl, 4-tert-butylphenyl,2-trifluoromethylphenyl, 4-trifluoromethylphenyl,4-(hydroxymethyl)phenyl, 4-(methoxymethyl)phenyl,4-(2-carboxylethyl)phenyl, 3-carboxylphenyl, 4-carboxylphenyl,4-methoxyphenyl, 3,4,5-trimethoxyphenyl, 4-carbamoylphenyl,4-methylthiophenyl, 4-(dimethylaminocarbonyl)phenyl,4-methylsulfonylphenyl, 4-acetylaminophenyl, 4-methylsulfinylphenyl,4-aminosulfonylphenyl, 4-cyanophenyl and 4-tetrazolylphenyl,particularly preferably 4-chlorophenyl.

The heterocyclic group optionally substituted by 1 to 5 substituent(s)selected from group B is that wherein the above-defined heterocyclicgroup is optionally substituted by 1 to 5 substituent(s), and includesunsubstituted heterocyclic group. The substituent(s) is(are) selectedfrom the above-defined halogen atom, cyano, nitro, the above-definedC₁₋₆ alkyl, the above-defined halogenated C₁₋₆ alkyl, the above-definedC₁₋₆ alkanoyl, —(CH₂)_(r)—COOR^(b1), —(CH₂)_(r)—CONR^(b1)R^(b2),—(CH₂)_(r) NR^(b1)R^(b2), —(CH₂)_(r)—NR^(b1)—COR^(b2),—(CH₂)_(r)—NHSO₂R^(b1), —(CH₂)_(r)—OR^(b1), —(CH₂)_(r)—SR^(b1),—(CH₂)_(r)—SO₂R^(b1) and —(CH₂)_(r)—SO₂NR^(b1)R^(b2) wherein R^(b1) andR^(b2) are each independently hydrogen atom or the above-defined C₁₋₆alkyl and r is 0 or an integer of 1 to 6.

Examples thereof include 2-pyridyl, 3-pyridyl, 4-pyridyl,3-fluoropyridin-4-yl, 3-chloropyridin-4-yl, 4-chloropyridin-3-yl,pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl, pyrrolyl,pyrazolyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, 2-thienyl,3-thienyl, furyl, oxazolyl, 2-methyloxazol-4-yl, isoxazolyl, thiazolyl,2-methylthiazol-4-yl, 2,5-dimethylthiazol-4-yl,2,4-dimethylthiazol-5-yl, isothiazolyl, thiadiazolyl, pyrrolinyl,pyrrolidinyl, 3-hydroxypyrrolidinyl, imidazolidinyl, azetidinyl,piperidyl, 3-hydroxypiperidino, 4-hydroxypiperidino,3,4-dihydroxypiperidino, 4-methoxypiperidino, 4-carboxypiperidino,4-(hydroxymethyl)piperidino, 2-oxopiperidino, 4-oxopiperidino,2,2,6,6-tetramethylpiperidino, 2,2,6,6-tetramethyl-4-hydroxypiperidino,N-methylpiperidin-4-yl, N-(tert-butoxycarbonyl)piperidin-4-yl,N-acetylpiperidin-4-yl, N-methylsulfonylpiperidin-4-yl, piperazinyl,4-methylpiperazinyl, 4-methylsulfonylpiperazinyl, morpholinyl,thiomorpholinyl, 1-oxothiomorpholin-4-yl, 1,1-dioxothiomorpholin-4-yl,tetrahydropyranyl, quinolyl, isoquinolyl, quinazolinyl, quinoxalyl,phthalazinyl, cinnolinyl, naphthyridinyl, 5,6,7,8-tetrahydroquinolyl,indolyl, benzimidazolyl, indolinyl, benzofuranyl, benzothienyl,benzoxazolyl, benzothiazolyl,

and the like.

The heterocyclic moiety is preferably a heterocyclic group which is a5-membered or a 6-membered monocyclic group. Examples thereof includepyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl, pyrrolyl,pyrazolyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, thienyl, furyl,oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, thiadiazolyl,pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl andtetrahydropyranyl, and the group B here is preferably the above-definedhalogen atom, the above-defined C₁₋₆ alkyl, the above-definedhalogenated C₁₋₆ alkyl, the above-defined C₁₋₆ alkanoyl,—(CH₂)_(r)—COOR^(b1), —(CH₂)_(r)—CONR^(b1)R^(b2) or —(CH₂)_(r)—OR^(b1).

Examples of heterocyclic group optionally substituted by 1 to 5substituent(s) selected from group B preferably include piperidino,4-methylpiperidino, 2,6-dimethylpiperidino, 4-hydroxypiperidino,1-piperazinyl, 1-(methylsulfonyl)piperidin-4-yl, 1-pyrrolidinyl,morpholino, 4-thiomorpholinyl, tetrahydropyranyl, pyridyl, thiazolyl,

Particularly preferably, it is piperidino, 4-methylpiperidino,2,6-dimethylpiperidino, 4-hydroxypiperidino, 1-piperazinyl,1-pyrrolidinyl, morpholino or 4-thiomorpholinyl at R^(a18),tetrahydropyranyl or 4-hydroxypiperidino at R^(a20), piperidino,4-hydroxypiperidino or 3,4-dihydroxypiperidino at R^(a21), pyridyl ormorpholino at R^(a24), pyridyl or 4-hydroxypiperidino at R^(a25),pyridyl or thiazolyl at R^(a26) and at R^(a27) and R^(a28), it is1-(methylsulfonyl)piperidin-4-yl, 3-hydroxypyrrolidinyl,3-hydroxypiperidino, 4-hydroxypiperidino, 3,4-dihydroxypiperidino,4-methoxypiperidino, 4-carboxypiperidino, 4-(hydroxymethyl)piperidino,2-oxopiperidino, 4-oxopiperidino, 2,2,6,6-tetramethylpiperidino,2,2,6,6-tetramethyl-4-hydroxypiperidino, 4-methylsulfonylpiperazinyl,1-oxothiomorpholin-4-yl or 1,1-dioxothiomorpholin-4-yl, and2-oxazolin-2-yl at R^(a22) and R^(a23).

The heterocyclic group optionally substituted by 1 to 5 substituent(s)selected from group D is that wherein the above-defined heterocyclicgroup is optionally substituted by 1 to 5 substituent(s), and includesunsubstituted heterocyclic group. The substituent(s) is(are) selectedfrom the substituent(s) of the above-mentioned group D (substituentsshown under (a) to (q)).

Examples of the group D here include the substituent(s) exemplified forC₆₋₁₄ aryl optionally substituted by 1 to 5 substituent(s) selected fromgroup D.

Examples of heterocyclic group optionally substituted by 1 to 5substituent(s) selected from group D include 2-pyridyl, 3-pyridyl,4-pyridyl, 3-fluoropyridin-4-yl, 3-chloropyridin-4-yl,4-chloropyridin-3-yl, pyrazinyl, pyrimidinyl, pyridazinyl,1,3,5-triazinyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,4-triazolyl,tetrazolyl, 2-thienyl, 3-thienyl, furyl, oxazolyl, 2-methyloxazol-4-yl,isoxazolyl, thiazolyl, 2-methylthiazol-4-yl, 2,5-dimethylthiazol-4-yl,2,4-dimethylthiazol-5-yl, isothiazolyl, thiadiazolyl, pyrrolinyl,pyrrolidinyl, imidazolidinyl, piperidyl, N-methylpiperidin-4-yl,N-(tert-butoxycarbonyl)piperidin-4-yl, N-acetylpiperidin-4-yl,N-methylsulfonylpiperidin-4-yl, piperazinyl, morpholinyl,thiomorpholinyl, tetrahydropyranyl, quinolyl, isoquinolyl, quinazolinyl,quinoxalyl, phthalazinyl, cinnolinyl, naphthyridinyl,5,6,7,8-tetrahydroquinolyl, indolinyl, benzimidazolyl, indolinyl,benzofuranyl, benzothienyl, benzoxazolyl, benzothiazolyl

and the like.

In addition, the heterocyclic group may be substituted at the 3-, 4-, 5-or 6-position of 2-pyridyl, at the 2-, 4-, 5- or 6-position of3-pyridyl, at the 2-, 3-, 5- or 6-position of 4-pyridinyl, at the 3-, 4-or 5-position of 2-thienyl, or at the 2-, 4- or 5-position of 3-thienyl,by fluorine atom, chlorine atom, bromine atom, nitro, methyl,tert-butyl, carboxyl, trifluoromethyl, hydroxymethyl, methoxymethyl,2-carboxylethyl, methoxy, carbamoyl, methylthio, dimethylaminocarbonyl,methylsulfonyl, amino or acetylamino.

At Z and Z′, the heterocyclic moiety is preferably a heterocyclic groupwhich is a 5-membered or 6-membered monocyclic group. Examples thereofinclude pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl,pyrrolyl, 2-oxopyrrolidinyl, 2-oxopiperidyl, pyrazolyl, imidazolyl,2-imidazolinyl, 2-oxoimidazolidinyl, 1,2,4-triazolyl, tetrazolyl,thienyl, furyl, oxazolyl, isoxazolyl, 2-oxazolinyl, thiazolyl,isothiazolyl, 1,1-dioxoisothiazolidinyl, thiadiazolyl, pyrrolidinyl,piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, tetrahydropyranyl,Δ²-1,2,4-oxadiazolyl, 5-oxo-Δ²-1,2,4-oxadiazolyl,5-oxo-Δ²-1,2,4-thiadiazolinyl and 2-oxo-3H-1,2,3,5-oxathiadiazolinyl.The group D here is preferably the above-defined halogen atom, nitro,the above-defined optionally substituted C₁₋₆ alkyl,—(CH₂)_(t)—COOR^(a19), —(CH₂)_(t)—CONR^(a27)R^(a28), —(CH₂)—OR^(a20),(CH₂) NR^(a29) CO—R^(a24), —(CH₂)_(t)—S(O)_(q)—R^(a25) or—(CH₂)_(t)—SO₂—NHR^(a26).

Examples of heterocyclic group optionally substituted by 1 to 5substituent(s) selected from group D preferably include piperidino,4-hydroxypiperidino, 2-oxopiperidin-1-yl, 1-piperazinyl, 1-pyrrolidinyl,2-oxopyrrolidin-1-yl, morpholino, 4-thiomorpholinyl,4-tetrahydropyranyl, 3-pyridyl, 2-pyrimidinyl, 2-imidazolin-2-yl,2-oxoimidazolidin-1-yl, 2-oxooxazolidin-1-yl, 5-tetrazolyl, 2-thiazolyl,4-thiazolyl, 5-thiazolyl, 2-methylthiazol-4-yl, 5-methylthiazol-2-yl,2-aminothiazol-4-yl, 3-methyl-1,2,4-oxadiazol-5-yl,1,1-dioxoisothiazolidin-2-yl, 4,4-dimethyl-Δ²-oxazolin-2-yl, 2-thienyl,5-chlorothiophen-2-yl, 5-methyloxazol-2-yl,5-oxo-Δ²-1,2,4-oxadiazolin-3-yl, 5-oxo-Δ²-1,2,4-thiadiazolin-3-yl and2-oxo-3H-1,2,3,5-oxathiazolin-4-yl.

Particularly preferably, it is pyridyl, pyrimidinyl, tetrazolyl,thienyl, piperidyl, 2-oxopiperidin-1-yl, 2-oxopyrrolidin-1-yl,2-imidazolin-2-yl, 2-oxoimidazolidin-1-yl, 2-oxooxazolidin-1-yl,2-methylthiazol-4-yl, 5-methylthiazol-2-yl, 2-aminothiazol-4-yl,3-methyl-1,2,4-oxadiazol-5-yl, 1,1-dioxoisothiazolidin-2-yl,4,4-dimethyl-Δ²-oxazolin-2-yl, 5-chlorothiophen-2-yl,5-methyloxazol-2-yl, 5-oxo-Δ²-1,2,4-oxadiazolin-3-yl,5-oxo-Δ²-1,2,4-thiadiazolin-3-yl or2-oxo-3H-1,2,3,5-oxathiadiazolin-4-yl, more preferably2-oxopiperidin-1-yl, 2-oxopyrrolidin-1-yl, 2-oxoimidazolidin-1-yl,2-oxooxazolidin-1-yl or 1,1-dioxoisothiazolidin-2-yl, most preferably2-oxopyrrolidin-1-yl.

The C₃₋₈ cycloalkyl optionally substituted by 1 to 5 substituent(s)selected from group C is that wherein the above-defined C₃₋₈ cycloalkylis optionally substituted by the 1 to 5 substituent(s) selected fromhydroxyl group, the above-defined halogen atom, the above-defined C₁₋₆alkyl and the above-defined C₁₋₆ alkoxy, which may be unsubstituted.Examples thereof include cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, cycloheptyl, 4-fluorocyclohexyl, 2-methylcyclopentyl,3-methylcyclohexyl, 4-methylcyclohexyl, 4,4-dimethylcyclohexyl,3,5-dimethylcyclohexyl, 4-tert-butylcyclohexyl, 4-hydroxycyclohexyl,4-methoxycyclohexyl and 2,3,4,5,6-pentafluorocyclohexyl.

The cycloalkyl moiety is preferably cyclopentyl or cyclohexyl,particularly preferably cyclohexyl.

At the ring Cy and ring Cy′, the C₃₋₈ cycloalkyl optionally substitutedby 1 to 5 substituent(s) selected from group C is preferablycyclopentyl, cyclohexyl, 4-fluorocyclohexyl, 4-methylcyclohexyl,4,4-dimethylcyclohexyl, 4-tert-butylcyclohexyl, 4-hydroxycyclohexyl or4-methoxycyclohexyl, more preferably cyclopentyl or cyclohexyl,particularly preferably cyclohexyl.

The C₃₋₈ cycloalkyl optionally substituted by 1 to 5 substituent(s)selected from the above group B is that wherein the above-defined C₃₋₈cycloalkyl is optionally substituted by 1 to 5 substituent(s), andincludes unsubstituted cycloalkyl. The substituents are selected fromthe above group B.

Specific examples thereof include cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, cycloheptyl, 4-fluorocyclohexyl, 2-methylcyclopentyl,3-methylcyclohexyl, 4-methylcyclohexyl, 4,4-dimethylcyclohexyl,3,5-dimethylcyclohexyl, 4-tert-butylcyclohexyl, 4-hydroxycyclohexyl,4-methoxycyclohexyl and 2,3,4,5,6-pentafluorocyclohexyl.

Also exemplified are those wherein cyclopentyl or cyclohexyl issubstituted by fluorine atom, chlorine atom, bromine atom, nitro,methyl, tert-butyl, carboxyl, trifluoromethyl, hydroxymethyl,methoxymethyl, 2-carboxylethyl, methoxy, carbamoyl, methylthio,dimethylaminocarbonyl, methylsulfonyl or acetylamino.

At cycloalkyl moiety, it is preferably cyclopropyl, cyclobutyl,cyclopentyl or cyclohexyl. As the C₃₋₈ cycloalkyl optionally substitutedby 1 to 5 substituent(s) selected from the above group B, it isparticularly preferably cyclopropyl, cyclobutyl, cyclohexyl or4-hydroxycyclohexyl at R^(a27) and R^(a28).

The C₃₋₈ cycloalkyl optionally substituted by 1 to 5 substituent(s)selected from group D is that wherein the above-defined C₃₋₈ cycloalkylis optionally substituted by 1 to 5 substituent(s), and includesunsubstituted cycloalkyl. The substituent(s) is(are) selected from thesubstituent(s) of the above-mentioned group D (substituents shown under(a) to (q)).

The group D here includes the substituents recited with regard to C₆₋₁₄aryl optionally substituted by 1 to 5 substituent(s) selected from groupD.

Examples thereof include cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, cycloheptyl, 4-fluorocyclohexyl, 2-methylcyclopentyl,3-methylcyclohexyl, 4-methylcyclohexyl, 4,4-dimethylcyclohexyl,3,5-dimethylcyclohexyl, 4-tert-butylcyclohexyl, 4-hydroxycyclohexyl,4-methoxycyclohexyl and 2,3,4,5,6-pentafluorocyclohexyl.

The group D may be, for example, cyclopentyl or cyclohexyl substitutedby fluorine atom, chlorine atom, bromine atom, nitro, methyl,tert-butyl, carboxyl, trifluoromethyl, hydroxymethyl, methoxymethyl,2-carboxylethyl, methoxy, carbamoyl, methylthio, dimethylaminocarbonyl,methylsulfonyl or acetylamino.

The cycloalkyl moiety is preferably cyclopentyl or cyclohexyl, and at Zand Z′, it is particularly preferably cyclohexyl.

The optionally substituted C₃₋₈ cycloalkenyl is that wherein theabove-defined C₃₋₈ cycloalkenyl is optionally substituted bysubstituent(s) selected from hydroxyl group, the above-defined halogenatom, the above-defined C₁₋₆ alkyl and the above-defined C₁₋₆ alkoxy,which may be unsubstituted. Examples thereof include cyclopropenyl,cyclobutenyl, cyclopentenyl, cyclopentadienyl, cyclohexenyl,4-fluoro-2-cyclohexenyl, 4-methyl-2-cyclohexenyl,4-methyl-3-cyclohexenyl, 2,4-cyclohexadien-1-yl, 2,5-cyclohexadien-1-yl,cycloheptenyl and cyclooctenyl and the like, but do not include aryl(e.g., phenyl) or completely saturated cycloalkyl.

The optionally substituted C₃₋₈ cycloalkenyl is particularly preferablycyclohexenyl at the ring Cy.

The C₆₋₁₄ aryl C₁₋₆ alkyl optionally substituted by 1 to 5substituent(s) selected from group B is that wherein the above-definedC₆₋₁₄ aryl C₁₋₆ alkyl is optionally substituted by 1 to 5substituent(s), and includes unsubstituted arylalkyl. The substituent(s)is(are) selected from the above-mentioned group B.

Examples thereof include benzyl, 1-naphthylmethyl, 2-naphthylmethyl,phenethyl, 3-phenylpropyl, 2-phenylpropyl, 3-fluorobenzyl,4-fluorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 2,4-dichlorobenzyl,3,5-dichlorobenzyl, pentafluorobenzyl, 4-methylbenzyl,4-tert-butylbenzyl, 2-trifluoromethylbenzyl, 4-trifluoromethylbenzyl,4-nitrobenzyl, 4-cyanobenzyl, 4-acetylbenzyl, 4-carboxylbenzyl,4-carbamoylbenzyl, 4-aminobenzyl, 4-dimethylaminobenzyl,4-acetylaminobenzyl, 4-(methylsulfonylamino)benzyl, 4-methoxybenzyl,3,4,5-trimethoxybenzyl, 4-methylthiobenzyl, 4-methylsulfonylbenzyl,4-aminosulfonylbenzyl, 3-nitro-4-methoxybenzyl and4-nitro-3-methoxybenzyl.

The C₆₋₁₄ aryl C₁₋₆ alkyl moiety is preferably benzyl or phenethyl,particularly preferably benzyl. The group B is preferably theabove-defined halogen atom, nitro, the above-defined C₁₋₆ alkyl, theabove-defined halogenated C₁₋₆ alkyl or —(CH₂)_(r)—OR^(b1). Examplesthereof include fluorine atom, chlorine atom, nitro, methyl, tert-butyl,trifluoromethyl, methoxy or trifluoromethyloxy, particularly preferablyfluorine atom or chlorine atom.

The specific C₆₋₁₄ aryl C₁₋₆ alkyl optionally substituted by 1 to 5substituent(s) selected from group B at R^(a12) and R^(a13) ispreferably benzyl, phenethyl, 3-chlorobenzyl, 4-chlorobenzyl,4-tert-butylbenzyl or 3-trifluoromethylbenzyl, it is preferably benzylat R^(a1), R^(a19), R^(a27), R^(a28), R^(a31) and R^(b5), it ispreferably benzyl, phenethyl, 4-fluorobenzyl, 2-chlorobenzyl,3-chlorobenzyl, 4-chlorobenzyl, 4-tert-butylbenzyl or4-trifluoromethylbenzyl at R^(a20), and 4-chlorobenzyl,3,5-dichlorobenzyl or 4-trifluoromethylbenzyl at R^(a22) and R^(a23).

It is particularly preferably benzyl at other substituents.

The C₆₋₁₄ aryl C₁₋₆ alkyl optionally substituted by 1 to 5substituent(s) selected from group D is that wherein the above-definedC₆₋₁₄ aryl C₁₋₆ alkyl is optionally substituted by 1 to 5substituent(s), and includes unsubstituted aryl. The substituent(s)is(are) selected from the substituent(s) of the above-mentioned group D(substituents shown under (a) to (q)).

Examples of group D include fluorine atom, chlorine atom, bromine atom,nitro, cyano, methyl, ethyl, propyl, isopropyl, tert-butyl,trifluoromethyl, hydroxymethyl, 2-hydroxyethyl, methoxymethyl,2-carboxylethyl, methoxycarbonylmethyl, ethoxycarbonylmethyl, acetyl,carboxyl, methoxycarbonyl, ethoxycarbonyl, carbamoyl,methylaminocarbonyl, isopropylaminocarbonyl, dimethylaminocarbonyl,diethylaminocarbonyl, (2-hydroxyethyl)aminocarbonyl,(carboxylmethyl)aminocarbonyl, hydroxyl group, methoxy, ethoxy,isopropyloxy, hydroxymethyloxy, carboxylmethyloxy,(dimethylaminocarbonyl)methyloxy, amino, methylamino, dimethylamino,diethylamino, acetylamino, methylsulfonylamino, methylthio,methylsulfonyl, methylsulfinyl, aminosulfonyl, methylaminosulfonyl anddimethylaminosulfonyl.

Examples of C₆₋₁₄ aryl C₁₋₆ alkyl optionally substituted by 1 to 5substituent(s) selected from group D include benzyl, 1-naphthylmethyl,2-naphthylmethyl, phenethyl, 3-phenylpropyl, 2-phenylpropyl,3-fluorobenzyl, 4-fluorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl,2,4-dichlorobenzyl, 3,5-dichlorobenzyl, 4-bromobenzyl, 4-nitrobenzyl,pentafluorobenzyl, 4-methylbenzyl, 4-tert-butylbenzyl,2-trifluoromethylbenzyl, 4-trifluoromethylbenzyl,4-(hydroxymethyl)benzyl, 4-(methoxymethyl)benzyl,4-(2-carboxylethyl)benzyl, 3-carboxylbenzyl, 4-carboxylbenzyl,4-methoxybenzyl, 3,4,5-trimethoxybenzyl, 4-carbamoylbenzyl,4-methylthiobenzyl, 4-(dimethylaminocarbonyl)benzyl,4-methylsulfonylbenzyl, 4-(acetylamino)benzyl, 4-cyanobenzyl,4-acetylbenzyl, 4-aminobenzyl, 4-dimethylaminobenzyl,4-(methylsulfonylamino)benzyl, 4-methylsulfinylbenzyl,4-aminosulfonylbenzyl, (3-nitro-4-methoxyphenyl)methyl and(4-nitro-3-methoxyphenyl)methyl.

At Z and Z′, the C₆₋₁₄ aryl C₁₋₆ alkyl moiety is preferably benzyl orphenethyl, and the group D here is preferably the above-defined halogenatom, nitro, the above-defined optionally substituted C₁₋₆ alkyl,—(CH₂)_(t)—COOR^(a19), —(CH₂)_(t)—CONR^(a27)R^(a28),—(CH₂)_(t)—OR^(a20), —(CH₂)_(t)—NR^(a29)CO—R^(a24),—(CH₂)_(t)—S(O)_(q)—R^(a25) or —(CH₂)_(t)—SO₂—NHR^(a26).

The C₆₋₁₄ aryl C₁₋₆ alkyl optionally substituted by 1 to 5substituent(s) selected from group D is preferably benzyl,3-fluorobenzyl, 4-fluorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl,3,5-dichlorobenzyl, 4-bromobenzyl, 4-nitrobenzyl, 4-methylbenzyl,4-tert-butylbenzyl, 2-trifluoromethylbenzyl, 4-trifluoromethylbenzyl,4-(hydroxymethyl)benzyl, 4-(methoxymethyl)benzyl,4-(2-carboxylethyl)benzyl, 3-carboxylbenzyl, 4-carboxylbenzyl,4-methoxybenzyl, 3,4,5-trimethoxybenzyl, 4-carbamoylbenzyl,4-methylthiobenzyl, 4-(dimethylaminocarbonyl)benzyl,4-methylsulfonylbenzyl, 4-acetylaminobenzyl, 4-methylsulfinylbenzyl or4-aminosulfonylbenzyl.

It is particularly preferably the above-defined halogen atom, theabove-defined optionally substituted C₁₋₆ alkyl, (CH₂)_(t)—COOR^(a19),(CH₂)_(t)—CONR^(a27)R^(a28), —(CH₂)_(t)—OR²⁰ or—(CH₂)_(t)—S(O)_(q)—R^(a25). Examples thereof include fluorine atom,chlorine atom, bromine atom, nitro, methyl, tert-butyl, carboxyl,trifluoromethyl, hydroxymethyl, methoxymethyl, 2-carboxylethyl, methoxy,carbamoyl, methylthio, dimethylaminocarbonyl, methylsulfonyl andacetylamino. It is more preferably fluorine atom, chlorine atom, methyl,tert-butyl, carboxyl, methoxy, carbamoyl, methylthio,dimethylaminocarbonyl or methylsulfonyl, most preferably fluorine atomor chlorine atom.

The heterocycle C₁₋₆ alkyl optionally substituted by 1 to 5substituent(s) selected from group B is that wherein the above-definedheterocycle C₁₋₆ alkyl is optionally substituted by 1 to 5substituent(s), and includes unsubstituted heterocycle C₁₋₆ alkyl. Thesubstituent(s) is(are) selected from the above-mentioned group B.

Examples thereof include 2-pyridylmethyl, 3-pyridylmethyl,2-chloropyridin-4-ylmethyl, 4-pyridylmethyl, pyrrolylmethyl,imidazolylmethyl, 2-thienylmethyl, 3-thienylmethyl, 2-furylmethyl,2-oxazolylmethyl, 5-isothiazolylmethyl, 2-methyloxazol-4-ylmethyl,2-thiazolylmethyl, 4-thiazolylmethyl, 5-thiazolylmethyl,2-methylthiazol-4-ylmethyl, 2-methylthiazol-5-ylmethyl,2,5-dimethylthiazol-4-ylmethyl, 4-methylthiazol-2-ylmethyl,2,4-dimethylthiazol-5-ylmethyl, 2-isothiazolylmethyl,2-pyrrolinylmethyl, pyrrolidinylmethyl, piperidylmethyl,4-piperidylmethyl, 1-methylpiperidin-4-ylmethyl,4-hydroxypiperidinomethyl, 3-hydroxypyrrolidinylmethyl,2-(4-hydroxypiperidino)ethyl,1-(tert-butoxycarbonyl)piperidin-4-ylmethyl,1-acetylpiperidin-4-ylmethyl, 1-methylsulfonylpiperidin-4-ylmethyl,piperazinylmethyl, morpholinomethyl, thiomorpholinylmethyl,1-tetrahydropyranylmethyl, 2-quinolylmethyl, 1-isoquinolylmethyl and thelike.

The heterocyclic moiety is preferably a heterocyclic group which is a5-membered or 6-membered monocyclic group. Examples thereof includepyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,3,5-triazinyl, pyrrolyl,pyrazolyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, thienyl, furyl,oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, thiadiazolyl,pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl andtetrahydropyranyl, and the alkyl moiety thereof is preferably straightchain alkyl having 1 to 4 carbon atoms. The group B here is preferablythe above-defined halogen atom, the above-defined C₁₋₆ alkyl, theabove-defined halogenated C₁₋₆ alkyl, the above-defined C₁₋₆ alkanoyl,—(CH₂)_(r)—COOR^(b1), —(CH₂)_(r)—CONR^(b1)R^(b2) or —(CH₂)_(r)—OR^(b1).

Examples of heterocycle C₁₋₆ alkyl optionally substituted by 1 to 5substituent(s) selected from group B preferably include 2-pyridylmethyl,3-pyridylmethyl, 2-chloropyridin-4-ylmethyl, 4-pyridylmethyl,piperidin-4-ylmethyl, 1-methylpiperidin-4-ylmethyl,2-(4-hydroxypiperidino)ethyl, 1-acetylpiperidin-4-ylmethyl,1-(tert-butoxycarbonyl)piperidin-4-ylmethyl,1-(methylsulfonyl)-piperidin-4-ylmethyl, 2-thiazolylmethyl,4-thiazolylmethyl, 2-methylthiazolin-4-ylmethyl,2,4-dimethylthiazolin-5-ylmethyl and 4-methylthiazol-2-ylmethyl.Particularly preferably, it is 2-pyridylmethyl, 3-pyridylmethyl,2-chloropyridin-4-ylmethyl, 4-pyridylmethyl, piperidin-4-ylmethyl,1-methylpiperidin-4-ylmethyl, 2-(4-hydroxypiperidino)ethyl,1-acetylpiperidin-4-ylmethyl,1-(tert-butoxycarbonyl)piperidin-4-ylmethyl,1-(methylsulfonyl)piperidin-4-ylmethyl, 2-methylthiazolin-4-ylmethyl,2,4-dimethylthiazolin-5-ylmethyl or 4-methylthiazol-2-ylmethyl atR^(a20), 2-pyridylmethyl at R^(a22) and R^(a23), and 4-pyridylmethyl or4-methylthiazol-2-ylmethyl at R^(a27) and R^(a28).

The heterocycle C₁₋₆ alkyl optionally substituted by 1 to 5substituent(s) selected from group D is that wherein the above-definedheterocycle C₁₋₆ alkyl is optionally substituted by 1 to 5substituent(s), and includes unsubstituted heterocycle C₁₋₆ alkyl. Thesubstituent(s) is(are) selected from the above-mentioned group D(substituents shown under (a) to (q)).

Examples of group D here include fluorine atom, chlorine atom, bromineatom, nitro, cyano, methyl, ethyl, propyl, isopropyl, tert-butyl,trifluoromethyl, hydroxymethyl, 2-hydroxyethyl, methoxymethyl,2-carboxylethyl, methoxycarbonylmethyl, ethoxycarbonylmethyl, acetyl,carboxyl, methoxycarbonyl, ethoxycarbonyl, carbamoyl,methylaminocarbonyl, isopropylaminocarbonyl, dimethylaminocarbonyl,diethylaminocarbonyl, (2-hydroxyethyl)aminocarbonyl,(carboxylmethyl)aminocarbonyl, hydroxyl group, methoxy, ethoxy,isopropyloxy, hydroxymethyloxy, carboxylmethyloxy,(dimethylaminocarbonyl)methyloxy, amino, methylamino, dimethylamino,diethylamino, acetylamino, methylsulfonylamino, methylthio,methylsulfonyl, methylsulfinyl, aminosulfonyl, methylaminosulfonyl anddimethylaminosulfonyl.

Examples of heterocycle C₁₋₆ alkyl optionally substituted by 1 to 5substituent(s) selected from group D include 2-pyridylmethyl,3-pyridylmethyl, 2-chloropyridin-4-ylmethyl, 4-pyridylmethyl,pyrrolylmethyl, imidazolylmethyl, 2-thienylmethyl, 3-thienylmethyl,2-furylmethyl, 2-oxazolylmethyl, 5-isothiazolylmethyl,2-methyloxazol-4-ylmethyl, 2-thiazolylmethyl, 4-thiazolylmethyl,5-thiazolylmethyl, 2-methylthiazol-4-ylmethyl,2-methylthiazol-5-ylmethyl, 2,5-dimethylthiazol-4-ylmethyl,4-methylthiazol-2-ylmethyl, 2,4-dimethylthiazol-5-ylmethyl,2-isothiazolylmethyl, 2-pyrrolinylmethyl, pyrrolidinylmethyl,piperidylmethyl, 4-piperidylmethyl, 1-methylpiperidin-4-ylmethyl,4-hydroxypiperidinomethyl, 2-(4-hydroxypiperidino)ethyl,1-(tert-butoxycarbonyl)piperidin-4-ylmethyl,1-acetylpiperidin-4-ylmethyl, 1-methylsulfonylpiperidin-4-ylmethyl,piperazinylmethyl, morpholinomethyl, thiomorpholinylmethyl,1-tetrahydropyranylmethyl, 2-quinolylmethyl, 1-isoquinolylmethyl, andthe like.

Preferable heterocyclic moiety at Z and Z′ is heterocylic group which is5-membered or 6-membered monocyclic group. Examples of the heterocyclicmoiety include pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl,1,3,5-triazinyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,4-triazolyl,tetrazolyl, thienyl, furyl, oxazolyl, isooxazolyl, thiazolyl,isothiazolyl, thiadiazolyl, pyrrolidinyl, piperidyl, piperazinyl,morpholinyl, thiomorpholinyl and tetrahydropyranyl, and the alkyl moietyis preferably straight chain alkyl having 1 to 4 carbon atoms,particularly methyl (i.e., methylene).

Preferable group D is the above-defined halogen atom, nitro, theabove-defined optionally substituted C₁₋₆ alkyl, —(CH₂)_(t)—COOR^(a19),—(CH₂)_(t)—CONR^(a27)R^(a28), —(CH₂)_(t)—OR^(a20),—(CH₂)_(t)—NR^(a29)COR^(a24), —(CH₂)_(t)—S(O)_(q)—R^(a25) or—(CH₂)_(t)—SO₂—NHR^(a26).

Preferable examples of heterocycle C₁₋₆ alkyl optionally substituted by1 to 5 substituent(s) selected from group D include 2-pyridylmethyl,3-pyridylmethyl, 2-chloropyridin-4-ylmethyl, 4-pyridylmethyl,piperidin-4-ylmethyl, 1-methylpiperidin-4-ylmethyl,4-hydroxypiperidinomethyl, 2-(4-hydroxypiperidino)ethyl,1-acetylpiperidin-4-ylmethyl,1-(tert-butoxycarbonyl)piperidin-4-ylmethyl,1-(methylsulfonyl)piperidin-4-ylmethyl, 2-thiazolylmethyl,4-thiazolylmethyl, 2-methylthiazolin-4-ylmethyl,2,4-dimethylthiazolin-5-ylmethyl and 4-methylthiazol-2-ylmethyl.

Particularly preferred is 4-hydroxypiperidinomethyl.

The C₃₋₈ cycloalkyl C₁₋₆ alkyl optionally substituted by 1 to 5substituent(s) selected from the above group B is that wherein theabove-defined C₃₋₈ cycloalkyl C₁₋₆ alkyl is optionally substituted by 1to 5 substituent(s), and includes unsubstituted cycloalkylalkyl. Thesubstituents are selected from the above group B.

Specific examples thereof include cyclopropylmethyl, cyclobutylmethyl,cyclopentylmethyl, cyclohexylmethyl, 2-(cyclopentyl)ethyl,2-(cyclohexyl)ethyl, cycloheptylmethyl, 4-fluorocyclohexylmethyl,2-methylcyclopentylmethyl, 3-methylcyclohexylmethyl,4-methylcyclohexylmethyl, 4,4-dimethylcyclohexylmethyl,3,5-dimethylcyclohexylmethyl, 4-tert-butylcyclohexylmethyl,4-hydroxycyclohexylmethyl, 4-methoxycyclohexylmethyl and2,3,4,5,6-pentafluorocyclohexylmethyl.

Also exemplified are those wherein cyclopentylmethyl or cyclohexylmethylis substituted by fluorine atom, chlorine atom, bromine atom, nito,methyl, tert-butyl, carboxyl, trifluoromethyl, hydroxymethyl,methoxymethyl, 2-carboxylethyl, methoxy, carbamoyl, methylthio,dimethylaminocarbonyl, methylsulfonyl or acetylamino.

At cycloalkyl moiety, it is preferably cyclopentylmethyl orcyclohexylmethyl, and at R^(a20), R^(a27) and R^(a28), it isparticularly preferably cyclohexylmethyl.

The carboxyl-protecting group only needs to be suitable for reactionconditions, and is capable of protecting and deprotecting and may be,for example, methyl; substituted methyl group such as methoxymethyl,methylthiomethyl, 2-tetrahydropyranyl, methoxyethoxymethyl,benzyloxymethyl, phenacyl, diacylmethyl, phthalimidomethyl etc.; ethyl;substituted ethyl group such as 2,2,2-trichloroethyl, 2-chloroethyl,2-(trimethylsilyl)ethyl, 2-methylthioethyl, 2-(p-toluenesulfonyl)ethyl,t-butyl etc.; benzyl; substituted benzyl group such as diphenylmethyl,triphenylmethyl, p-nitrobenzyl, 4-picolyl, p-methoxybenzyl,2-(9,10-dioxo)anthrylmethyl etc.; silyl group such as trimethylsilyl,t-butyldimethylsilyl, phenyldimethylsilyl etc.; and the like.

Preferred are industrially effective protecting groups and specificallypreferred as R^(a36) are methyl and ethyl.

In formula [I], X is preferably

wherein each symbol is as defined above.

G¹, G², G³ and G⁴ are each preferably (C—R¹), (C—R²), (C—R³ and (C—R⁴),G⁵ is preferably a nitrogen atom, and G⁶, G⁸ and G⁹ are preferably acarbon atom. G⁷ is preferably C(—R⁷) or unsubstituted nitrogen atom,wherein R⁷ is preferably hydrogen atom.

A preferable combination is G² of (C—R²) and G⁶ of a carbon atom,particularly preferably G² of (C—R²), G⁶ of a carbon atom and G⁵ of anitrogen atom, most preferably G² of (C—R²), G⁶ of a carbon atom, G⁵ ofa nitrogen atom and G⁷ of unsubstituted nitrogen atom.

In formulas [I] and [II], 1 to 4 of G¹ to G⁹ in the moiety

is(are) preferably a nitrogen atom, specifically preferably

particularly preferably

more preferably

most preferably

It is also a preferable embodiment wherein the

moiety is aromatic ring.

R¹ and R³ are preferably hydrogen atom or —OR^(a6) (R^(a6) is as definedabove), particularly preferably hydrogen atom. R² is preferablycarboxyl, —COOR^(a1), —CONR^(a2)R^(a3), —SO₂R^(a7) (each symbol is asdefined above) or heterocyclic group having 1 to 4 heteroatom(s)selected from an oxygen atom, a nitrogen atom and a sulfur atom,particularly preferably carboxyl, —COOR^(a1) or —SO₂R^(a7), morepreferably carboxyl or —COOR^(a1), most preferably carboxyl. R⁴ ispreferably hydrogen atom.

R^(a1) is preferably optionally substituted C₁₋₆ alkyl.

When R² is carboxyl or —COOR^(a1), at least one of R¹, R³ and R⁴ ispreferably hydroxyl group, halogen atom (particularly fluorine atom,chlorine atom) or —OR^(a6) (wherein R^(a6) is preferably hydrogen atomor methyl).

The ring Cy and ring Cy′ are preferably cyclopentyl, cyclohexyl,cycloheptyl, tetrahydrothiopyranyl or piperidino, particularlypreferably cyclopentyl, cyclohexyl or cycloheptyl, more preferablycyclohexyl.

The ring A and ring A′ are preferably phenyl, pyridyl, pyrazinyl,pyrimidinyl, pyridazinyl, cyclohexyl, cyclohexenyl, furyl or thienyl,particularly preferably phenyl, pyridyl, pyrazinyl, pyrimidinyl orpyridazinyl, more preferably phenyl or pyridyl, and most preferablyphenyl.

The ring B and ring B′ are preferably C₁₋₆ aryl or heterocyclic group,specifically preferably, phenyl, pyridyl, pyrazinyl, pyrimidinyl,pyridazinyl, 1,3,5-triazinyl, pyrrolyl, pyrazolyl, imidazolyl,1,2,4-triazolyl, tetrazolyl, thienyl, furyl, oxazolyl, isoxazolyl,thiazolyl, isothiazolyl or thiadiazolyl, particularly preferably phenyl,pyridyl, pyrimidinyl, 1,3,5-triazinyl or thiazolyl, more preferably,phenyl, pyridyl or thiazolyl, and most preferably phenyl or thiazolyl.

With regard to R⁵ and R⁶, one of them is preferably hydrogen atom andthe other is halogen atom, particularly fluorine atom. Alternatively,the both are preferably hydrogen atoms. When ring A is phenyl, R⁵ and R⁶preferably are present at an ortho position from G⁶. The same applies toR⁵′ and R⁶′.

Y is preferably —(CH₂)_(m)—O—(CH₂)_(n)—, —NHCO₂—, —CONH—CHR^(a14)—,—(CH₂)_(m)—NR^(a12)—(CH₂)_(n)—,—CONR^(a13)—(CH₂)_(n)—(CH₂)_(m)—CR^(a15)R^(a16)—(CH₂)_(n)— or—(CH₂)_(n)—NR^(a12)—CHR^(a15)— (each symbol is as defined above), morepreferably, —(CH₂)_(m)—O—(CH₂)_(n)— or—O—(CH₂)_(m)—CR^(a15)R^(a16)—(CH₂)_(n)—, most preferably —(CH₂)_(m)—O—(CH₂)_(n)—.

The l, m and n are preferably 0 or an integer of 1 to 4, particularlypreferably 0, 1 or 2, at Y. In —(CH₂)_(m)—O—(CH₂)_(n)—, m=n=0 or m=0 andn=1 is more preferable, most preferably m=0 and n=1. In—O—(CH₂)_(m)—CR^(a15)R^(a16)—(CH₂)_(n)—, m=n=0, m=0 and n=1, m=1 and n=0or m=1 and n=1 is more preferable, most preferably m=0 and n=1.

When Y is —O—(CH₂)_(m)—CR^(a15)R^(a16)—(CH₂)_(n)—, R^(a16) is preferablyhydrogen atom, R^(a15) is preferably

wherein the

moiety is preferably symmetric. The preferable mode of n, ring B, Z andw and the preferable mode of n′, ring B′, Z′ and w′ are the same.

When ring A is phenyl, X or Y is preferably present at the para-positionrelative to G⁵. When ring B and ring B′ are phenyl,

-   -   Z is preferably present at the ortho or meta-position relative        to Y. It is preferable that the 3-position on phenyl have one        substituent or the 2-position and the 5-position on phenyl each        have one substituent.

When ring B is bonded to Y as pyridin-2-yl, Z is preferably substitutedat the 3-position and 6-position of pyridyl; when it is bonded to Y aspyridin-3-yl, Z is preferably substituted at the 2-position and5-position of pyridyl; and when it is bonded to Y as pyridin-4-yl, Z ispreferably substituted at the 2-position and 5-position of pyridyl.

When ring B is thiazolyl, Y is preferably substituted at the 5-position,and Z is preferably substituted at the 2-position, the 4-position or the2-position and the 4-position. Similarly, when ring B′ is thiazolyl,(CH₂)_(n′) is also preferably substituted at the 5-position, and Z′ ispreferably substituted at the 2-position, the 4-position or the2-position and the 4-position.

Z and Z′ are preferably group D, “C₆₋₁₄ aryl optionally substituted by 1to 5 substituent(s) selected from group D” or “heterocyclic groupoptionally substituted by 1 to 5 substituent(s) selected from group D”,particularly preferably group D or “C₆₋₁₄ aryl optionally substituted by1 to 5 substituent(s) selected from group D”.

More preferably, they are the above-defined halogen atom, nitro, theabove-defined optionally substituted C₁₋₆ alkyl, —(CH₂)_(t)—COOR^(a19),—(CH₂)_(t)—CONR^(a27)R^(a28), —(CH₂)_(t)—OR^(a20),—(CH₂)_(t)—NR^(a29)CO—R^(a24), —(CH₂)_(t)—S(O)_(q)—R^(a25) or—(CH₂)_(t)—SO₂—NHR^(a26), or C₆₋₁₄ aryl or heterocyclic group optionallysubstituted by these.

With regard to Z and Z′, the preferable mode of group D that directlysubstitutes each ring B and ring B′ and the preferable mode of group Dthat substitutes C₆₋₁₄ aryl, C₃₋₈ cycloalkyl, C₆₋₁₄ aryl C₁₋₆ alkyl orheterocyclic group are the same, wherein they may be the same with ordifferent from each other.

Specific examples of the substituent preferably include fluorine atom,chlorine atom, bromine atom, nitro, cyano, methyl, ethyl, propyl,isopropyl, tert-butyl, trifluoromethyl, hydroxymethyl, 2-hydroxyethyl,methoxymethyl, 2-carboxylethyl, methoxycarbonylmethyl,ethoxycarbonylmethyl, carbamoylmethoxymethyl,(dimethylaminocarbonyl)methoxymethyl, acetyl, isovaleryl, carboxyl,methoxycarbonyl, ethoxycarbonyl, carbamoyl, methylaminocarbonyl,hydroxyaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl,isopropylaminocarbonyl, butylaminocarbonyl, isobutylaminocarbonyl,tert-butylaminocarbonyl, (4-hydroxybutyl)aminocarbonyl,(1-hydroxypropan-2-yl)aminocarbonyl,(2,3-dihydroxypropyl)-aminocarbonyl,(1,3-dihydroxypropan-2-yl)aminocarbonyl, methoxyaminocarbonyl,2-{2-(methoxy)ethoxy]ethyl}aminocarbonyl, N-ethyl-N-methylaminocarbonyl,N-methyl-N-propylaminocarbonyl, N-isopropyl-N-methylaminocarbonyl,dimethylaminocarbonyl, diethylaminocarbonyl,(2-hydroxyethyl)aminocarbonyl,(2-hydroxy-2-methylpropan-2-yl)aminocarbonyl,(carboxylmethyl)aminocarbonyl, hydroxyl group, methoxy, ethoxy,propyloxy, isopropyloxy, butyloxy, isopentyloxy, 2-isopentenyloxy,3-isohexenyloxy, 4-methyl-3-pentenyloxy, 2-propynyloxy,trifluoromethyloxy, hydroxymethyloxy, carboxylmethyloxy,(dimethylaminocarbonyl)-methyloxy, amino, methylamino, dimethylamino,diethylamino, acetylamino, N-acetyl-N-methylamino,N-acetyl-N-ethylamino, N-acetyl-N-propylamino,N-acetyl-N-isopropylamino, N-ethylcarbonyl-N-methylamino,N-ethyl-N-(ethylcarbonyl)amino, ureido, isopropylcarbonylamino,isobutylcarbonylamino, tert-butylcarbonylamino,(ethylamino)carbonylamino, (isopropylamino)-carbonylamino,(dimethylamino)carbonylamino, (4-hydroxypiperidino)carbonylamino,[(4-hydroxypiperidino)methyl]-carbonylamino,[(3-hydroxypyrrolidinyl)methyl]carbonylamino, methylsulfonylamino,isopropylsulfonylamino, N-(methylsulfonyl)-N-methylamino,N-(ethylsulfonyl)-N-methylamino, N-(isopropylsulfonyl)-N-methylamino,N-(methylsulfonyl)-N-ethylamino, N-(methylsulfonyl)-N-propylamino,N-(ethylsulfonyl)-N-ethylamino, methylthio, methylsulfonyl,isopropylsulfonyl, isobutylsulfonyl, methylsulfinyl, isopropylsulfinyl,aminosulfonyl, methylaminosulfonyl, dimethylaminosulfonyl,isopropylaminosulfonyl, tert-butylaminosulfonyl, hydroxyamidino, phenyl,3-fluorophenyl, 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl,2,4-difluorophenyl, 3,4-difluorophenyl, 3,4-dichlorophenyl,3,5-dichlorophenyl, 4-chloro-3-fluorophenyl, 4-chloro-2-fluorophenyl,4-bromophenyl, 4-nitrophenyl, 4-cyanophenyl, 4-methylphenyl,4-ethylphenyl, 4-propylphenyl, 4-isopropylphenyl, 4-tert-butylphenyl,2-trifluoromethylphenyl, 4-trifluoromethylphenyl,4-(hydroxymethyl)phenyl, 4-(2-hydroxyethyl)phenyl,4-(methoxymethyl)phenyl, 4-(2-carboxylethyl)phenyl,4-(methoxycarbonylmethyl)phenyl, 4-(ethoxycarbonylmethyl)phenyl,4-acetylphenyl, 3-carboxylphenyl, 4-carboxylphenyl,4-(methoxycarbonyl)phenyl, 4-(ethoxycarbonyl)phenyl, 4-carbamoylphenyl,4-(methylaminocarbonyl)phenyl, 4-(isopropylaminocarbonyl)phenyl,4-(dimethylaminocarbonyl)phenyl, 4-(diethylaminocarbonyl)phenyl,4-[(2-hydroxyethyl)aminocarbonyl]phenyl,4-[(carboxylmethyl)aminocarbonyl]phenyl, 4-hydroxyphenyl,4-methoxyphenyl, 3,4,5-trimethoxyphenyl, 4-ethoxyphenyl,4-propyloxyphenyl, 4-isopropyloxyphenyl, 4-butyloxyphenyl,4-isopentyloxyphenyl, 4-(2-isopentenyloxy)phenyl,4-(3-isohexenyloxy)phenyl, 4-(4-methyl-3-pentenyloxy)phenyl,4-(2-propynyloxy)phenyl, 4-(trifluoromethyloxy)phenyl,4-(hydroxymethyloxy)phenyl, 4-(carboxylmethyloxy)phenyl,4-[(dimethylaminocarbonyl)methyloxy]phenyl, 4-aminophenyl,4-(methylamino)phenyl, 4-(dimethylaminophenyl), 4-(diethylamino)-phenyl,4-(acetylamino)phenyl, N-acetyl-N-methylamino,4-(N-acetyl-N-methylamino)phenyl, 4-(N-acetyl-N-ethylamino)phenyl,4-(N-acetyl-N-propylamino)phenyl, 4-(N-acetyl-N-isopropylamino)phenyl,4-(N-ethylcarbonyl-N-methylamino)phenyl,4-[N-ethyl-N-(ethylcarbonyl)amino]phenyl, 4-(methylsulfonylamino)phenyl,4-(methylthio)phenyl, 4-(methylsulfonyl)phenyl,4-(methylsulfinyl)phenyl, 4-(aminosulfonyl)phenyl,4-(methylaminosulfonyl)phenyl, 4-(dimethylaminosulfonyl)phenyl,4-(tert-butylaminosulfonyl)phenyl, tetrazol-5-ylphenyl, cyclohexyl,benzyl, 4-chlorobenzyl, phenethyl, benzyloxy, 4-fluorobenzyloxy,2-chlorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy,4-tert-butylbenzyloxy, 4-trifluoromethylbenzyloxy, phenethyloxy,2-thienyl, 2-thiazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl,6-fluoropyridin-3-yl, 5-fluoropyridin-2-yl, 6-chloropyridin-3-yl,6-methylpyridin-3-yl, 2-pyrimidinyl, 5-tetrazolyl, piperidino,2-oxopiperidin-1-yl, 2-oxopyrrolidin-1-yl, 2-imidazolin-2-yl,2-oxoimidazolidin-1-yl, 2-oxooxazolidin-1-yl, 2-methylthiazol-4-yl,5-methylthiazol-2-yl, 2-aminothiazol-4-yl,3-methyl-1,2,4-oxadiazol-5-yl, 1,1-dioxoisothiazolidin-2-yl,4,4-dimethyl-Δ²-oxazolin-2-yl, 5-chlorothiophen-2-yl,5-methyloxazol-2-yl, 5-oxo-Δ²-1,2,4-oxadiazolin-3-yl,5-oxo-Δ²-1,2,4-thiadiazolin-3-yl, 2-oxo-3H-1,2,3,5-oxathiadiazolin-4-yl,4-hydroxypiperidinomethyl, piperidinocarbonyl,4-hydroxypiperidinocarbonyl, 3,4-dihydroxypiperidinocarbonyl,1-piperazinylcarbonyl, 1-pyrrolidinylcarbonyl, morpholinocarbonyl,4-thiomorpholinylcarbonyl, phenoxy, 2,4-dichlorophenoxy,tetrahydropyranyloxy, 2-pyridylmethyloxy, 3-pyridylmethyloxy,2-chloropyridin-4-ylmethyloxy, 4-pyridylmethyloxy, 2-piperidylmethyloxy,3-piperidylmethyloxy, 4-piperidylmethyloxy,1-methylpiperidin-4-ylmethyloxy, 1-acetylpiperidin-4-ylmethyloxy,1-(tert-butoxycarbonyl)piperidin-4-ylmethyloxy,1-(methylsulfonyl)piperidin-4-ylmethyloxy, 2-methylthiazolin-4-yloxy,2,4-dimethylthiazolin-5-yloxy, dimethylaminocarbonyl-methyloxy,piperidinocarbonylmethyloxy, 4-hydroxypiperidino-carbonylmethyloxy,2-methylthiazol-4-yl, (2-methylthiazol-4-yl)methyloxy,(2,4-dimethylthiazol-5-yl)methyloxy, benzoyl, 3-fluorobenzoyl,4-chlorobenzylamino, 3,5-dichlorobenzylamino,4-trifluoromethylbenzylamino, 2-pyridylmethylamino, benzoylamino,4-chlorobenzoylamino, 4-trifluoromethylbenzoylamino,3,5-dichlorobenzoylamino, 3-nitro-4-methoxybenzoylamino,4-nitro-3-methoxybenzoylamino, 3-pyridylcarbonylamino,4-morpholinocarbonylamino, 2-oxazolinylamino,4-hydroxypiperidinosulfonyl, methylphenylsulfonylamino,2-thiazolylaminosulfonyl, 2-pyridylaminosulfonyl, benzylaminocarbonyl,N-benzyl-N-methylaminocarbonyl, (4-pyridylmethyl)aminocarbonyl or(cyclohexylmethyl)aminocarbonyl, 2-hydroxyethyloxy, 3-hydroxypropyloxy,2-methoxyethoxy, 2-(2-methoxyethoxy)ethoxy, azetidinylcarbonyl,3-hydroxypyrrolidinylcarbonyl, 3-hydroxypiperidinocarbonyl,4-hydroxypiperidinocarbonyl, 3,4-dihydroxypiperidinocarbonyl,4-methoxypiperidinocarbonyl, 4-carboxypiperidinocarbonyl,4-(hydroxymethyl)piperidinocarbonyl, 2-oxopiperidinocarbonyl,4-oxopiperidinocarbonyl, 2,6-dimethylpiperidinocarbonyl,2,2,6,6-tetramethylpiperidinocarbonyl,2,2,6,6-tetramethyl-4-hydroxypiperidinocarbonyl,1-oxothiomorpholin-4-ylcarbonyl, 1,1-dioxothiomorpholin-4-ylcarbonyl,1-(methylsulfonyl)piperidin-4-ylaminocarbonyl,4-methylsulfonylpiperazinylcarbonyl, 4-methylpiperazinylcarbonyl,N,N-bis(2-hydroxyethyl)aminocarbonyl, phenylaminocarbonyl,cyclopropylaminocarbonyl, cyclobutylaminocarbonyl,cyclohexylaminocarbonyl, 4-hydroxycyclohexylaminocarbonyl,4-methylthiazol-2-ylmethylaminocarbonyl,2-(4-hydroxypiperidino)ethyloxy, 2-pyridylmethylaminocarbonyl,3-pyridylmethylaminocarbonyl, N-methyl-N-(4-pyridylmethyl)aminocarbonyl,cyclohexylmethyloxy, 4-hydroxypiperidinocarbonylmethyloxy and4-methylthiazol-2-ylmethyloxy.

Particularly preferable examples of the substituent include fluorineatom, chlorine atom, bromine atom, nitro, cyano, methyl, hydroxymethyl,carboxyl, carbamoyl, methylaminocarbonyl, isopropylaminocarbonyl,dimethylaminocarbonyl, diethylamino-carbonyl,(2-hydroxylethyl)aminocarbonyl, (carboxymethyl)-aminocarbonyl, methoxy,2-isopentenyloxy, 2-propynyloxy, methylthio, methylamino, dimethylamino,acetylamino, N-acetyl-N-methylamino, N-acetyl-N-ethylamino,N-acetyl-N-propylamino, N-acetyl-N-isopropylamino,N-ethylcarbonyl-N-methylamino, N-ethyl-N-(ethylcarbonyl)amino,methylsulfonylamino, methylsulfonyl, aminosulfonyl,dimethylaminosulfonyl, tert-butylaminosulfonyl, phenyl, 3-fluorophenyl,4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3,5-dichlorophenyl,4-nitrophenyl, 4-methylphenyl, 4-tert-butylphenyl,4-trifluoromethylphenyl, 4-(methoxymethyl)-phenyl,4-(2-hydroxylethyl)phenyl, 3-carboxylphenyl, 4-carboxylphenyl,4-methoxyphenyl, 4-carbamoylphenyl, 4-methylthiophenyl,4-(dimethylaminocarbonyl)phenyl, 4-methylsulfonylphenyl, benzyl,phenethyl, benzyloxy, 4-fluorobenzyloxy, 4-chlorobenzyloxy, 2-thiazolyl,3-pyridyl, 4-pyridyl, 4-pyridylmethyloxy, 2-piperidylmethyloxy,3-piperidylmethyloxy, 4-piperidylmethyloxy,1-methylpiperidin-4-ylmethyloxy, 1-acetylpiperidin-4-ylmethyloxy,2-chloropiperidin-4-ylmethyloxy,1-(methylsulfonyl)piperidin-4-ylmethyloxy, 2-methylthiazol-4-yl,(2-methylthiazol-4-yl)methyloxy, (2,4-dimethylthiazol-5-yl)methyloxy,5-tetrazolyl, 3-fluorobenzoyl, piperidinocarbonyl,4-hydroxylpiperidinocarbonyl, 1-pyrrolidinylcarbonyl,morpholinocarbonyl, 4-thiomorpholinylcarbonyl, benzylaminocarbonyl,N-benzyl-N-methylaminocarbonyl, (4-pyridylmethyl)aminocarbonyl and(cyclohexylmethyl)aminocarbonyl.

Most preferable substituents are fluorine atom, chlorine atom, methyl,hydroxymethyl, carboxyl, carbamoyl, methylaminocarbonyl,dimethylaminocarbonyl, methoxy, methylamino, acetylamino, aminosulfonyl,dimethylaminosulfonyl, tert-butylaminosulfonyl, phenyl, 3-fluorophenyl,4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3,5-dichlorophenyl,4-methylphenyl, 4-tert-butylphenyl, 4-trifluoromethylphenyl,4-carboxylphenyl, 4-methoxyphenyl, 4-carbamoylphenyl,4-methylthiophenyl, 4-(dimethylaminocarbonyl)phenyl,4-methylsulfonylphenyl and 2-oxopyrrolidin-1-yl.

The w is preferably 1 or 2, r and t are preferably 0, 1 or 2,particularly preferably 0 or 1, more preferably 0, p is preferably 1,and q is preferably 0 or 2.

In formula [I], when X is

wherein each symbol is as defined above and w is 2 or above, one of Z ispreferably C₆₋₁₄ aryl optionally substituted by 1 to 5 substituent(s)selected from group D or heterocyclic group optionally substituted by 1to 5 substituent(s) selected from group D, particularly preferably C₆₋₁₄aryl optionally substituted by 1 to 5 substituent(s) selected from groupD.

When ring B is phenyl, w is 2 and phenyl is bonded to Y at the1-position, one of the most preferable embodiments is that wherein Z isbonded to the 2-position and 5-position of phenyl, Z at the 2-positionis “C₆₋₁₄ aryl optionally substituted by 1 to 5 substituent(s) selectedfrom group D” and Z at the 5-position is “heterocyclic group optionallysubstituted by 1 to 5 substituent(s) selected from group D”.

The pharmaceutically acceptable salt may be any as long as it forms anon-toxic salt with a compound of the above-mentioned formula [I] or[II]. Such salt can be obtained by reacting the compound with aninorganic acid, such as hydrochloric acid, sulfuric acid, phosphoricacid, hydrobromic acid and the like, or an organic acid, such as oxalicacid, malonic acid, citric acid, fumaric acid, lactic acid, malic acid,succinic acid, tartaric acid, acetic acid, trifluoroacetic acid,gluconic acid, ascorbic acid, methylsulfonic acid, benzylsulfonic acid,meglumine acid and the like, or an inorganic base, such as sodiumhydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide,ammonium hydroxide and the like, or an organic base, such asmethylamine, diethylamine, triethylamine, triethanolamine,ethylenediamine, tris(hydroxymethyl)methylamine, guanidine, choline,cinchonine and the like, with an amino acid, such as lysine, arginine,alanine and the like. The present invention encompasses water-retainingproduct, hydrate and solvate of each compound.

The compounds of the above-mentioned formula [I] or [II] have variousisomers. For example, E compound and Z compound are present as geometricisomers, and when the compound has an asymmetric carbon, an enantiomerand a diastereomer are present due to the asymmetric carbon. A tautomermay be also present. The present invention encompasses all of theseisomers and mixtures thereof.

The present invention also encompasses prodrug and metabolite of eachcompound.

A prodrug means a derivative of the compound of the present invention,which is capable of chemical or metabolic decomposition, which showsinherent efficacy by reverting to the original compound afteradministration to a body, and which includes salts and complexes withouta covalent bond.

When the inventive compound is used as a pharmaceutical preparation, theinventive compound is generally admixed with pharmaceutically acceptablecarriers, excipients, diluents, binders, disintegrators, stabilizers,preservatives, buffers, emulsifiers, aromatics, coloring agents,sweeteners, thickeners, correctives, solubilizers, and other additivessuch as water, vegetable oil, alcohol such as ethanol, benzyl alcoholand the like, polyethylene glycol, glycerol triacetate, gelatin,lactose, carbohydrate such as starch and the like, magnesium stearate,talc, lanolin, petrolatum and the like, and prepared into a dosage formof tablets, pills, powders, granules, suppositories, injections, eyedrops, liquids, capsules, troches, aerosols, elixirs, suspensions,emulsions, syrups and the like, which can be administered systemicallyor topically and orally or parenterally.

While the dose varies depending on the age, body weight, generalcondition, treatment effect, administration route and the like, it isfrom 0.1 mg to 1 g for an adult per dose, which is given one to severaltimes a day.

The prophylaxis of hepatitis C means, for example, administration of apharmaceutical agent to an individual found to carry an HCV by a testand the like but without a symptom of hepatitis C, or to an individualwho shows an improved disease state of hepatitis after a treatment ofhepatitis C, but who still carries an HCV and is associated with a riskof recurrence of hepatitis.

The therapeutic agent for hepatitis C of the present invention isexpected to provide a synergestic effect when concurrently used withother antiviral agents, antiinflammatory agents or immunostimulants.

The medicaments with the prospect of synergestic effect include, forexample, interferon-α, interferon-β, interferon-γ, interleukin-2,interleukin-8, interleukin-10, interleukin-12, TNFα, recombinant ormodified products thereof, agonists, antibodies, vaccines, ribozymes,antisense nucleotides and the like.

As evidenced in the combination therapy of anti-HIV agents, which isalso called a cocktail therapy, the combined use of various anti-virusagents againt viruses showing frequent genetic mutations is expected toshow effect for suppressing emergence and increase of drug tolerantviruses. For example, 2 or 3 agents from HCV-IRES inhibitors, HCV-NS3protease inhibitors, HCV-NS2NS3 protease inhibitors, HCV-NS5A inhibitorsand HCV polymerase inhibitor may be used in combination. Specifically,the combined use with Ribavirin®, interferon-α (IFN-α, Roferon®, IntronA®, Sumiferon®, MultiFeron®, Infergen®, Omniferon®, Pegasys®, PEG-IntronA®), interferon-β (Frone®, Rebif®, AvoneX®, IFNβMOCHIDA®), interferon-ω,1-β-L-ribofuranosyl-1H-1,2,4-triazole-3-carboxamide,16α-bromo-3β-hydroxy-5α-androstan-17-one, 1H-imidazole-4-ethanamidedihydrochloride, HCV ribozyme Heptazyme®, polyclonal antibody Civacir®,lactoferrin GPX-400,(1S,2R,8R,8aR)-1,2,8-trihydroxyoctahydroindolizidinium chloride, HCVvaccine (MTH-68/B, Innivax C®, Engerix B®, antisense oligonucleotideISIS-14803, HCV-RNA transcriptase inhibitor VP-50406,tetrachlorodecaoxide (high concentration Oxoferin®),tetrahydrofuran-3-yl(S)-N-3-[3-(3-methoxy-4-oxazol-5-ylphenyl)ureido]benzylcarbamate,4-amino-2-ethoxymethyl-α,α-dimethyl-1H-imidazo[4,5-c]quinoline-1-ethanol,interleukin-2 (Proleukin®), thymosin α1 and the like is exemplified,wherein (R) shows product names.

Furthermore, the combined use with the compounds disclosed inJP-A-08-268890, JP-A-10-101591, JP-A-07-069899, WO99/61613 and the likeas HCV IRES inhibitors; the compounds disclosed in WO98/22496,WO99/07733, WO99/07734, WO00/09543, WO00/09558, WO01/59929, WO98/17679,EP932617, WO99/50230, WO00/74768, WO97/43310, U.S. Pat. No. 5,990,276,WO01/58929, WO01/77113, WO02/8198, WO02/8187, WO02/8244, WO02/8256,WO01/07407, WO01/40262, WO01/64678, WO98/46630, JP-A-11-292840,JP-A-10-298151, JP-A-11-127861, JP-A-2001-103993, WO98/46597,WO99/64442, WO00/31129, WO01/32961, WO93/15730, U.S. Pat. No. 7,832,236,WO00/200400, WO02/8251, WO01/16379, WO02/7761 and the like as HCVprotease inhibitors; the compounds disclosed in WO97/36554, U.S. Pat.No. 5,830,905, WO97/36866, U.S. Pat. No. 5,633,388, WO01/07027,WO00/24725 and the like as HCV helicase inhibitors; the compoundsdisclosed in WO00/10573, WO00/13708, WO00/18231, WO00/06529, WO02/06246,WO01/32153, WO01/60315, WO01/77091, WO02/04425, WO02/20497, WO00/04141and the like as HCV polymerase inhibitors; the compounds disclosed inWO01/58877, JP-A-11-180981, WO01/12214 and the like as interferonagonists or enhancers; and the like is also exemplified.

Inasmuch as HCV is known to be a virus associated with many geneticmutations, a compound effective for many genotypes is one of thepreferable modes. If a compound ensures high blood concentration whenadministered as a pharmaceutical agent to an animal infected with HCV,it is also one of the preferable modes. From these aspects, a compoundhaving high inhibitory activity on both HCV type 1a and type 1b and highblood concentration, such as2-{4-[2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylicacid hydrochloride, is particularly preferable.

The fused ring compound of the formula [I] or [II] of the presentinvention can be administered to mammals inclusive of human for thepurpose of prevention or treatment of hepatitis C or inhibition ofhepatitis C virus polymerase. The fused ring compound of the presentinvention can be also administered to mammals inclusive of human alongwith at least one pharmaceutical agent (hereinafter combination drug)selected from an antiviral agent other than the compound of the formula[I], an antiinflammatory agent and an immunostimulant for the purpose ofprevention or treatment of hepatitis C or inhibition of hepatitis Cvirus polymerase. In the case of combined administration, the compoundof the present invention can be administered simultaneously with thecombination drug or administered at certain time intervals. In the caseof combined administration, a pharmaceutical composition containing thecompound of the present invention and a combination drug can beadministered. Alternatively, a pharmaceutical composition containing thecompound of the present invention and a pharmaceutical compositioncontaining a combination drug may be administered separately. Theadministration route may be the same or different.

In the case of a combined administration, the compound of the presentinvention can be administered once a day or several times a day in asingle dose of 0.1 mg to 1 g, or may be administered in a smaller dose.The combination drug can be administered in a dose generally used forthe prevention or treatment of hepatitis C or in a smaller dose.

Examples of other antiviral agent include interferons (interferon α,interferon β, interferon γ etc.), Ribavirin(1-β-D-ribofuranosyl-1H-1,2,4-triazole-3-carboxamide) and the like.

Examples of the production method of the compound to be used for thepractice of the present invention are given in the following. However,the production method of the compound of the present invention is notlimited to these examples.

Even if no directly corresponding disclosure is found in the followingProduction Methods, the steps may be modified for efficient productionof the compound, such as introduction of a protecting group into afunctional group with deprotection in a subsequent step, and changingthe order of Production Methods and steps.

The treatment after reaction in each step may be conventional ones, forwhich typical methods, such as isolation and purification,crystallization, recrystallization, silica gel chromatography,preparative HPLC and the like, can be appropriately selected andcombined.

Production Method 1

In this Production Method, a benzimidazole compound is formed from anitrobenzene compound.Production Method 1-1

wherein Hal is halogen atom, such as chlorine atom, bromine atom and thelike, R^(c1) is halogen atom, such as chlorine atom, bromine atom andthe like, or hydroxyl group, and other symbols are as defined above.Step 1

A compound [1] obtained by a conventional method or a commerciallyavailable compound [1] is reacted with amine compound [2] in a solventsuch as N,N-dimethylformamide (DMF), acetonitrile, tetrahydrofuran(THF), toluene and the like in the presence or absence of a base such aspotassium carbonate, triethylamine, potassium t-butoxide and the like atroom temperature or with heating to give compound [3].

Step 2

The compound [3] is hydrogenated in a solvent such as methanol, ethanol,THF, ethyl acetate, acetic acid, water and the like in the presence of acatalyst such as palladium carbon, palladium hydroxide, platinum oxide,Raney nickel and the like at room temperature or with heating to givecompound [4]. In addition, compound [3] is reduced with a reducing agentsuch as zinc, iron, tin(II) chloride, sodium sulfite and the like, orreacted with hydrazine in the presence of iron(III) chloride to givecompound [4]. The compound [4] can be also obtained by reacting compound[3] with sodium hydrosulfite under alkaline conditions.

Step 3

The compound [4] is condensed with carboxylic acid compound [5] in asolvent such as DMF, acetonitrile, THF, chloroform, ethyl acetate,methylene chloride, toluene and the like using a condensing agent suchas dicyclohexylcarbodiimide,1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride,diphenylphosphoryl azide and the like and, where necessary, addingN-hydroxysuccinimide, 1-hydroxybenzotriazole and the like to give amidecompound [6]. Alternatively, amide compound [6] can be obtained fromcompound [5] as follows. The carboxylic acid compound [5] is convertedto an acid halide derived with thionyl chloride, oxalyl chloride and thelike, or an active ester (e.g., mixed acid anhydride derived with ethylchlorocarbonate and the like), which is then reacted in the presence ofa base, such as triethylamine, potassium carbonate, pyridine and thelike, or in an amine solvent, such as pyridine and the like, to giveamide compound [6].

Step 4

The compound [6] is heated in a solvent such as ethanol, methanol,toluene, DMF, chloroform and the like or without a solvent in thepresence of an acid such as acetic acid, formic acid, hydrochloric acid,dilute sulfuric acid, phosphoric acid, polyphosphoric acid,p-toluenesulfonic acid and the like, a halogenating agent such as zincchloride, phosphorus oxychloride, thionyl chloride and the like or acidanhydride such as acetic anhydride and the like, to allow cyclization togive compound [1-2].

Production Method 1-2

This Production Method is an alternative method for producing compound[I-2].

wherein each symbol is as defined above.Step 1

The compound [3] obtained in the same manner as in Step 1 of ProductionMethod 1-1 is subjected to amide condensation with compound [5] in thesame manner as in Step 3 of Production Method 1-1 to give compound [7].

Step 2

The compound [7] is reduced in the same manner as in Step 2 ofProduction Method 1-1 to give compound [8].

Step 3

The compound [8] is subjected to cyclization in the same manner as inStep 4 of Production Method 1-1 to give compound [I-2].Production Method 1-3

wherein R^(c2) is alkyl such as methyl, ethyl and the like, and othersymbols are as defined above.

The compound [4] is reacted with imidate compound [9] in a solvent suchas methanol, ethanol, acetic acid, DMF, THF, chloroform and the like atroom temperature or with heating to give compound [I-2].

In addition, compound [4] may be reacted with aldehyde compound [10] ina solvent such as acetic acid, formic acid, acetonitrile, DMF,nitrobenzene, toluene and the like in the presence or absence of anoxidizing agent such as benzofuroxan, manganese dioxide,2,3-dichloro-5,6-dicyano-p-benzoquinone, iodine, potassium ferricyanideand the like with heating to give compound [I-2].

Alternatively, compound [4] and carboxylic acid compound [11] may beheated to allow reaction in the presence of polyphosphoric acid,phosphoric acid, phosphorus oxychloride, hydrochloric acid and the liketo give compound [I-2].

Production Method 2

In this Production Method, conversion of the substituents (R¹, R², R³,R⁴) on the benzene ring of benzimidazole is shown. While a method ofconverting R² when R¹, R³ and R⁴ are hydrogen atoms is shown, thisProduction Method is applicable irrespective of the position ofsubstitution.

Production Method 2-1

Conversion of Carboxylic Acid Ester Moiety to Amide

wherein E is a single bond, —(CH₂)—, —O—(CH₂)— or —NH—(CH₂)_(s)—(wherein s is an integer of 1 to 6), R^(c3), R^(c4) and R^(c5) areC₁₋₆alkyl, and other symbols are as defined above.Step 1

The compound [I-2-1] obtained in the same manner as in theabove-mentioned Production Method is subjected to hydrolysis in asolvent such as methanol, ethanol, THF, dioxane and the like, or in amixed solvent of these solvents and water under basic conditions withsodium hydroxide, potassium hydroxide, potassium carbonate, lithiumhydroxide and the like or under acidic conditions with hydrochloricacid, sulfuric acid and the like to give compound [I-2-2].

Step 2

The compound [I-2-2] is reacted with compound [12] in the same manner asin Step 3 of Production Method 1-1 to give compound [I-2-3].

Production Method 2-2

Conversion of cyano group to substituted amidino group

wherein each symbol is as defined above.

The compound [I-2-4] obtained in the same manner as in theabove-mentioned Production Method is reacted with hydroxylamine in asolvent such as water, methanol, ethanol, THF, DMF and the like to givecompound [I-2-5]. When a salt of hydroxylamine such as hydrochloride andthe like is used, the reaction is carried out in the presence of a basesuch as sodium hydrogencarbonate, sodium hydroxide, triethylamine andthe like.

Production Method 2-3

Conversion of sulfonic acid ester moiety to sulfonic acid

wherein R^(c6) is C₁₋₆ alkyl, and other symbols are as defined above.

The compound [I-2-6] obtained in the same manner as in theabove-mentioned Production Method is reacted with iodide salt such assodium iodide, lithium iodide and the like, bromide salt such as sodiumbromide, trimethylammonium bromide and the like, amine such as pyridine,trimethylamine, triazole and the like, phosphine such astriphenylphosphine and the like in a solvent such as DMF, dimethylsulfoxide (DMSO), acetonitrile, methanol, ethanol, water and the likewith heating to give compound [I-2-7].

Production Method 3

This Production Method relates to convertion of the substituent(s) onphenyl group at the 2-position of benzimidazole. This Production Methodcan be used even when phenyl is a different ring.

Production Method 3-1

Conversion of hydroxyl group to ether

wherein R^(c7) is optionally substituted alkyl corresponding to R^(a11),G¹ is a single bond, *—(CH₂)_(n)—, *—(CH₂)_(n)—O—, *—(CH₂)—CO— or*—(CH₂)_(m)—CR^(a15)R^(a16))—(CH₂)_(n)—, wherein * show the side to bebonded to R^(c1) and other symbols are as defined above.

When R^(c1) of compound [13] is halogen atom, compound [I-2-8] obtainedin the same manner as in the above-mentioned Production Method isreacted with compound [13] in a solvent such as DMF, DMSO, acetonitrile,ethanol, THF and the like in the presence of a base such as sodiumhydride, sodium hydroxide, potassium hydroxide, potassium carbonate,sodium ethoxide, potassium t-butoxide and the like at room temperatureor with heating to give compound [II-2-1].

When R^(c1) of compound [13] is hydroxyl group, the hydroxyl group ofcompound [13] is converted to halogen atom with thionyl chloride,phosphorus tribromide, carbon tetrabromide-triphenylphosphine and thelike and reacted with compound [I-2-8] by the aforementioned method togive compound [II-2-1]. In this case, compound [I-2-8] may be subjectedto Mitsunobu reaction with compound [13] in a solvent such as DMF,acetonitrile, THF and the like using triphenylphosphine-diethylazodicarboxylate and the like to give compound [II-2-1].

The compound [I-2-9] can be obtained in the same manner from compound[I-2-8] and compound [14].

Production Method 3-2

Conversion of nitro to substituted amino group

wherein R^(c8) is C₁₋₆alkyl, G² is *—(CH₂)— or *—CHR^(a15), G³ is —CO—,*—CO₂—, *—CONH— or —SO₂—, and other symbols are as defined above.Step 1

The nitro compound [I-2-10] obtained in the same manner as in theabove-mentioned Production Method is reacted in the same manner as inStep 2 of Production Method 1-1 to give compound [I-2-11].

Step 2

The compound [I-2-11] is alkylated with compound [15] in the same manneras in Production Method 3-1 to give compound [II-2-2].

Step 3

When G³ of compound [16] is —CO—, —CO₂— or —CONH—, compound [I-2-11] isacylated with compound [16] in the same manner as in Step 3 ofProduction Method 1-1 to give compound [II-2-3].

When G³ of compound [16] is —SO₂—, sulfonylation is conducted usingsulfonyl halide instead of acid halide used in Step 3 of ProductionMethod 1-1 to give compound [II-2-3].

The compound [I-2-11] is acylated with compound [17] in the same manneras above to give compound [I-2-12].

This Production Method is applied in the same manner as above to givedisubstituted compounds (tertiary amine) of compound [II-2-2], compound[II-2-3] and compound [I-2-12].

Production Method 3-3

Conversion of carboxylic acid ester moiety to amide

wherein R^(c9) is C₁₋₆ alkyl, G⁴ is #—(CH₂)_(n)—, #—(CH₂)_(n)—NH— or#—CHR^(a14)— wherein # shows the side that is bounded to amine and othersymbols are as defined above.Step 1

The compound [I-2-13] obtained in the same manner as in theabove-mentioned Production Method is reacted in the same manner as inStep 1 of Production Method 2-1 to give compound [I-2-14].

Step 2

The compound [I-2-14] is reacted with compound [18] in the same manneras in Step 2 of Production Method 2-1 to give compound [II-2-4].

The compound [I-2-15] is obtained from compound [I-2-14] and compound[19] in the same manner as above.

Production Method 4

In this Production Method, additional substituent(s) is(are) introducedinto ring B on phenyl group that substitutes the 2-position ofbenzimidazole. This Production Method is applicable even when phenyl isa different ring.

Production Method 4-1

Direct Bonding of Ring Z″ to Ring B

wherein ring Z″-M is aryl metal compound, ring Z″ moiety is optionallysubstituted C₆₋₁₄ aryl or optionally substituted heterocyclic groupcorresponding to substituent Z, and the metal moiety contains boron,zinc, tin, magnesium and the like, such as phenylboronic acid, w″ is 0,1 or 2, and other symbols are as defined above.

The compound [II-2-5] obtained in the same manner as in theabove-mentioned Production Method is reacted with aryl metal compound[20] in a solvent such as DMF, acetonitrile, 1,2-dimethoxyethane, THF,toluene, water and the like in the presence of a palladium catalyst suchas tetrakis(triphenylphosphine)-palladium,bis(triphenylphosphine)palladium(II) dichloride, palladiumacetate-triphenylphosphine and the like, a nickel catalyst such asnickel chloride, [1,3-bis(diphenylphosphino)-propane]nickel(II) chlorideand the like, and a base such as potassium carbonate, potassiumhydrogencarbonate, sodium hydrogen-carbonate, potassium phosphate,triethylamine and the like at room temperature or with heating, to givecompound [II-2-6].

Production Method 4-2

Conversion of hydroxyl group to ether

wherein R^(c10) is —R^(a20) or —(CH₂)_(p)—COR^(a21) corresponding tosubstituent Z, and other symbols are as defined above.

The compound [II-2-7] obtained in the same manner as in theabove-mentioned Production Method is reacted with compound [21] in thesame manner as in Production Method 3-1 to give compound [II-2-8].

Production Method 4-3

Synthesis in advance of ring B part such as compound [13] in ProductionMethod 3-1

wherein R^(c11) is leaving group such as chlorine atom, bromine atom,iodine atom, trifluoromethanesulfonyloxy and the like, R^(c12) isformyl, carboxyl or carboxylic acid ester such as methoxycarbonyl,ethoxycarbonyl, tert-butoxycarbonyl and the like, and other symbols areas defined above.Step 1

Commercially available compound [22] or compound [22] obtained by aconventional method is reacted with aryl metal compound [20] in the samemanner as in Production Method 4-1 to give compound [23].

Step 2

The compound [23] obtained in the same manner as in the above-mentionedProduction Method is reduced according to a conventional method to givecompound [24].

For example, compound [23] is reacted with in a solvent such asmethanol, ethanol, THF and the like in the presence of a reducing agentsuch as lithium aluminum hydride, sodium borohydride and the like undercooling to heating to give compound [24].

Step 3

The compound [24] obtained in the same manner as in the above-mentionedProduction Method is reacted in a solvent such as 1,4-dioxane, diethylether, THF, dichloromethane, chloroform, toluene and the like with ahalogenating agent, such as phosphorus pentachloride, phosphorustribromide, thionyl chloride and the like, to give compound [25]. For anaccerelated reaction, the reaction may be carried out in the presence ofa tertiary amine such as DMF, pyridine and the like, or under heating.

Step 4

The compound [24] or [25] obtained in the same manner as in theabove-mentioned Production Method is reacted with compound [I-2-8] inthe same manner as in Production Method 3-1 to give compound [II-2-9].Production Method 4-4

wherein M′ is a metal such as magnesium, lithium, zinc and the like, andother symbols are as defined above.Step 1

Commercially available compound [41] or compound [41] obtained by aconventional method is converted to aryl metal reagent by a conventionalmethod to give compound [42].

For example, when M′ is magnesium, magnesium is reacted with compound[41] in a solvent such as THF, diethyl ether, benzene, toluene and thelike, preferably THF, from cooling to heating preferably at −100° C. to100° C. to give compound [42].

Step 2

The compound [42] obtained in the same manner as in the above-mentionedProduction Method is reacted with compound [43] to give compound [44].

The compound [42] is reacted in a solvent such as diethyl ether,benzene, toluene, THF and the like, preferably THF, from cooling to roomtemperature, preferably at −100° C. to 30° C. to give compound [44].

Step 3

The compound [44] obtained in the same manner as in the above-mentionedProduction Method is halogenated in the same manner as in Step 3 ofProduction Method 4-3 to give compound [45].

The compound [44] is reacted with thionyl chloride and pyridinepreferably in toluene solvent to give compound [45].

When compound [45] is symmetric, namely, when the ring B-(Z)w moiety andthe ring B′-(Z′)w′ moiety are the same, compound [42] is reacted withformate such as methyl formate, ethyl formate and the like, preferablyethyl formate, in a solvent such as diethyl ether, benzene, toluene, THFand the like, preferably THF, from cooling to room temperature,preferably at −100° C. to 30° C., to give compound [45].

Production Method 4-5

Method including steps to introduce a protecting group into a functionalgroup

wherein R^(c13) is carboxylic acid protecting group such as tert-butyland the like, R^(c14) is carboxylic acid protecting group such as methyland the like and other symbols are as defined above.Step 1

Commercially available compound [26] or compound [26] obtained by aconventional method is protected by a conventional method to givecompound [27].

For example, when R^(c13) is tert-butyl, compound [26] is converted toacid halide with thionyl chloride, oxalyl chloride and the like in asolvent such as THF, chloroform, dichloromethane, toluene and the like,and reacted with potassium tert-butoxide to give compound [27].

As used herein, R^(c13) may be a different protecting group as long asit is not removed during the Step 2 or Step 3 but removed in Step 4without affecting —CO₂R^(c14).

Step 2

The methyl group of compound [27] obtained in the same manner as in theabove-mentioned Production Method is converted to bromomethyl withN-bromosuccinimide and N,N′-azobisisobutyronitrile and reacted withcompound [I-2-16] in the same manner as in Production Method 3-1 to givecompound [II-2-10].

Step 3

The compound [II-2-10] obtained in the same manner as in theabove-mentioned Production Method is reacted with aryl metal compound[20] in the same manner as in Production Method 4-1 to give compound[II-2-11].

Step 4

The R^(c13) of the compound [II-2-11] obtained in the same manner as inthe above-mentioned Production Method is removed by a conventionalmethod to give compound [II-2-12].

The protecting group of carboxylic acid can be removed by a conventionaldeprotection method according to the protecting group. In this Step, theconditions free from reaction of R^(c14) are preferable. For example,when R^(c13) is tert-butyl, compound [II-2-11] is treated withtrifluoroacetic acid in a solvent such as dichloromethane, chloroformand the like to give compound [II-2-12].

Step 5

The compound [II-2-12] obtained in the same manner as in theabove-mentioned Production Method is subjected to amide condensationwith compound [28] in the same manner as in Step 3 of Production Method1-1 to give compound [II-2-13].

Step 6

The compound [II-2-13] obtained in the same manner as in theabove-mentioned Production Method is deprotected in the same manner asin Step 1 of Production Method 2-1 to give compound [II-2-14].

As used herein, R^(c14) is preferably a protecting group that does notreact during the Step 1 through Step 5 but removed in this Step.

For example, when R^(c14) is methyl, compound [II-2-13] is reacted in analcohol solvent such as methanol, ethanol, n-propanol, isopropanol andthe like or a mixed solvent of alcohol solvent and water in the presenceof a base such as potassium carbonate, sodium carbonate, lithiumhydroxide, sodium hydroxide, potassium hydroxide and the like fromcooling to heating for deprotection, followed by acidifying the reactionsolution to give compound [II-2-14].Production Method 4-6

wherein g is an integer of 1 to 5, and other sumbols are as definedabove.Step 1

The compound [I-2-16] obtained by the above-mentioned Production Methodis reacted with toluene derivative [41] in the same manner as in Step 2of Production Method 4-5 to give compound [II-2-17].

Step 2

The compound [II-2-17] obtained by the above-mentioned Production Methodis reacted with aryl metal compound [20] in the same manner as inProduction Method 4-1 to give compound [II-2-18].

Step 3

The compound [II-2-18] obtained by the above-mentioned Production Methodis reduced in the same manner as in Step 2 of Production Method 1-1 togive compound [II-2-19].

Step 4

The compound [II-2-19] obtained by the above-mentioned Production Methodis amide condensed with compound [42] in the same manner as in Step 3 ofProduction Method 1-1 and subjected to cyclization in the same manner asin Step 1 of Production Method 1-1 to give compound [II-2-20].

Step 5

The compound [II-2-20] obtained by the above-mentioned Production Methodis hydrolyzed in the same manner as in Step 1 of Production Method 2-1to give compound [II-2-21].Production Method 4-7

wherein each symbol is as defined above.Step 1

Commercially available product or compound [46] obtained by aconventional method is reacted with compound [20] in the same manner asin Production Method 4-1 to give compound [47].

Step 2

The compound [47] obtained in the same manner as in the above-mentionedProduction Method is reduced in the same manner as in theabove-mentioned Production Method 4-3 Step 2 to give compound [48].

Step 3

The compound [48] obtained in the same manner as in the above-mentionedProduction Method is reduced in the same manner as in theabove-mentioned Production Method 1-1 Step 2 to give compound [49].

Step 4

The compound [49] obtained in the same manner as in the above-mentionedProduction Method is reacted with compound [42] in a solvent such asDMF, acetonitrile, THF, chloroform, ethyl acetate, methylene chlorideand toluene to give compound [50]. To enhance the reaction selectivityfor amino group, acetic acid and sodium acetate may be added in anequivalent amount ratio.

Step 5

The compound [50] obtained in the same manner as in the above-mentionedProduction Method is subjected to cyclization reaction in the samemanner as in the above-mentioned Production Method 1-1 Step 1 to givecompound [51].

Step 6

The compound [51] obtained in the same manner as in the above-mentionedProduction Method is halogenated in the same manner as in theabove-mentioned Production Method 4-3 Step 3 to give compound [52].

Step 7

The compound [52] obtained in the same manner as in the above-mentionedProduction Method is reacted in the same manner as in theabove-mentioned Production Method 3-1 with compound [I-2-16] obtained inthe same manner as in the above-mentioned Production Method to givecompound [II-2-20].

Step 8

The compound [II-2-20] obtained in the same manner as in theabove-mentioned Production Method is hydrolyzed in the same manner as inthe above-mentioned Production Method 2-1 Step 1 to give compound[II-2-21].

Production Method 5

Formation of indole ring

wherein R^(C15) is protecting group such as trimethylsilyl,tert-butyldimethylsilyl, tert-butyldiphenylsilyl and the like, and othersymbols are as defined above.Step 1

The compound [29] obtained in the same manner as in the above-mentionedProduction Method or conventional method is reacted with compound [30]in a solvent such as DMF, acetonitrile, 1,2-dimethoxyethane, THF,toluene, water and the like using a palladium catalyst such astetrakis(triphenylphosphine)palladium,bis(triphenylphosphine)palladium(II) dichloride, palladiumacetate-triphenylphosphine and the like, a copper catalyst such ascopper(I) iodide and the like or a mixture thereof, and in the presenceof a base such as potassium carbonate, potassium hydrogencarbonate,sodium hydrogencarbonate, potassium phosphate, triethylamine and thelike to give compound [31].

Step 2

The compound [31] obtained in the same manner as in the above-mentionedProduction Method is reacted in an alcohol solvent such as methanol,ethanol and the like or a mixed solvent of an alcohol solvent and asolvent such as DMF, acetonitrile, THF, chloroform, dichloromethane,ethyl acetate, methylene chloride, toluene and the like in the presenceof a base such as potassium carbonate, sodium carbonate, lithiumhydroxide, sodium hydroxide, potassium hydroxide, lithium hydride,sodium hydride, potassium hydride and the like at room temperature orwith heating for deprotection, and reacted with compound [32] obtainedin the same manner as in Step 1 of Production Method 1-1 in the samemanner as in Step 1 of Production Method 5 to give compound [33].

step 3

The compound [33] obtained in the same manner as in the above-mentionedProduction Method was subjected to cyclization in a solvent such as DMF,acetonitrile, THF, chloroform, dichloromethane, ethyl acetate, methylenechloride, toluene and the like in the presence of a copper catalyst suchas copper(I) iodide and the like or a palladium catalyst such aspalladium(II) chloride and the like at room temperature or with heatingto give compound [II-2-15].

Production Method 6

Formation of imidazo[1,2-a]pyridine ring

wherein R^(c16) and R^(c17) are each independently alkyl, such asmethyl, ethyl and the like, and other symbols are as defined above.Step 1

The compound [34] obtained by the above-mentioned Production Method or aconventional method is subjected to amide condensation with compound[35] in the same manner as in Step 3 of Production Method 1-1 to givecompound [36].

Step 2

The compound [36] obtained by the above-mentioned Production Method isreacted with Grignard reagent [37] obtained by a conventional method togive compound [38].

Alternatively, an acid halide of compound [34] may be used instead ofcompound [36].

Step 3

The compound [38] obtained by the above-mentioned Production Method issubjected to halogenation by a conventional method to give compound[39].

For example, when Hal is a bromine atom, compound [38] is reacted withbromine under cooling or at room temperature in a solvent such as DMF,acetonitrile, THF, chloroform, dichloromethane, ethyl acetate, tolueneand the like to give compound [39].

Alternatively, a halogenating agent such as hypohalite (e.g.,hypochlorite and the like), N-bromosuccinimide and the like may be usedinstead of bromine for halogenation.

Step 4

The compound [39] obtained by the above-mentioned Production Method issubjected to cyclization with compound [40] obtained by a conventionalor known method (JP-A-8-48651) in the presence of a base such aspotassium carbonate, sodium carbonate, lithium hydroxide, sodiumhydroxide, potassium hydroxide, lithium hydride, sodium hydride,potassium hydride and the like in a solvent or without a solvent at roomtemperature or with heating to give compound [II-2-16].

In the compounds of the formulas [I] and [II], a desired heterocyclicgroup can be formed according to a method similar to the methodsdisclosed in known publications. Examples of such heterocyclic group andreference publications are recited in the following.

-   5-oxo-Δ²-1,2,4-oxadiazolin-3-yl (or    2,5-dihydro-5-oxo-4H-1,2,4-oxadiazol-3-yl),    5-oxo-Δ²-1,2,4-thiadiazolin-3-yl (or    2,5-dihydro-5-oxo-4H-1,2,4-thiadiazol-3-yl),    2-oxo-Δ³-1,2,3,5-oxathiadiazolin-4-yl (or    2-oxo-Δ³-1,2,4-oxathiadiazol-4-yl): Journal of Medicinal Chemistry,    39(26), 5228-35, 1996,-   5-oxo-Δ²-1,2,4-triazolin-3-yl: J Org Chem, 61(24), 8397-8401, 1996,-   1-oxo-Δ³-1,2,3,5-thiatriazolin-4-yl: Liebigs Ann Chem, 1376, 1980,-   3-oxo-Δ⁴-1,2,4-oxadiazolin-5-yl: EP145095,-   5-oxo-Δ²-1,3,4-oxadiazolin-2-yl: J Org Chem, 20, 412, 1955,-   5-oxo-Δ³-1,2,4-dioxazolin-3-yl: J Prakt Chem, 314, 145, 1972,-   3-oxo-Δ⁴-1,2,4-thiadiazolin-5-yl: JP-A-61-275271,-   5-oxo-Δ³-1,2,4-dithiazolin-3-yl: J Org Chem, 61(19), 6639-6645,    1996,-   2-oxo-Δ⁴-1,3,4-dioxazolin-5-yl: J Org Chem, 39, 2472, 1974,-   2-oxo-Δ⁴-1,3,4-oxathiazolin-5-yl: J Med Chem, 35(20), 3691-98, 1992,-   5-oxo-Δ²-1,3,4-thiadiazolin-2-yl: J Prakt Chem, 332(1), 55, 1990,-   5-oxo-Δ²-1,4,2-oxathiazolin-3-yl: J Org Chem, 31, 2417, 1966,-   2-oxo-Δ⁴-1,3,4-dithiazolin-5-yl: Tetrahedron Lett, 23, 5453, 1982,-   2-oxo-Δ⁴-1,3,2,4-dioxathiazolin-5-yl: Tetrahedron Lett, 319, 1968,-   3,5-dioxoisooxazolidin-4-yl: Helv Chim Acta, 1973, 48, 1965,-   2,5-dioxoimidazolidin-4-yl: Heterocycles, 43(1), 49-52, 1996,-   5-oxo-2-thioxoimidazolidin-4-yl: Heterocycles, 5, 391, 1983,-   2,4-dioxooxazolidin-5-yl: J Am Chem Soc, 73, 4752, 1951,-   4-oxo-2-thioxooxazolidin-5-yl: Chem Ber, 91, 300, 1958,-   2,4-dioxothiazolidin-5-yl: JP-A-57-123175,-   4-oxo-2-thioxothiazolidin-5-yl: Chem Pharm Bull, 30, 3563, 1982,

The Production Methods shown in the above-mentioned Production Methods 2to 4 can be used for the synthesis of compounds other than benzimidazoleof the formulas [I] and [II], such as compounds [II-2-15] and [II-2-16].

The compounds of the formulas [I], [II] and [III],4-(4-fluorophenyl)-5-hydroxymethyl-2-methylthiazole and4-(4-fluorophenyl)-5-chloromethyl-2-methylthiazole and productionmethods thereof of the present invention are explained in detail in thefollowing by way of Examples. It is needless to say that the presentinvention is not limited by these Examples.

EXAMPLE 1 Production of ethyl2-[4-(3-bromophenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate

Step 1: Production of ethyl 4-chloro-3-nitrobenzoate

4-Chloro-3-nitrobenzoic acid (300 g) was dissolved in ethyl alcohol(1500 ml) and concentrated sulfuric acid (100 ml) was added withice-cooling. The mixture was refluxed under heating for 7 hr. Thereaction mixture was poured into ice-cold water and the precipitatedcrystals were collected by filtration to give the title compound (332 g,yield 97%).

¹H-NMR (300 MHz, CDCl₃): 8.50(1H, d, J=2.1 Hz), 8.16(1H, dd, J=8.4, 2.1Hz), 7.63(1H, d, J=8.4 Hz), 4.43(2H, q, J=7.5 Hz), 1.42(3H, t, J=7.5 Hz)

Step 2: Production of ethyl 4-cyclohexylamino-3-nitrobenzoate

Ethyl 4-chloro-3-nitrobenzoate (330 g) obtained in the previous step wasdissolved in acetonitrile (1500 ml), and cyclohexylamine (220 g) andtriethylamine (195 g) were added. The mixture was refluxed under heatingovernight. The reaction mixture was poured into ice-cold water and theprecipitated crystals were collected by filtration to give the titlecompound (400 g, yield 94%).

¹H-NMR (300 MHz, CDCl₃): 8.87(1H, d, J=2.1 Hz), 8.35-8.46(1H, m),8.02(1H, dd, J=9.1, 2.1 Hz), 6.87(1H, d, J=9.1 Hz), 4.35(2H, q, J=7.1Hz), 3.65-3.50(1H, m), 2.14-1.29(10H, m), 1.38(3H, t, J=7.1 Hz)

Step 3: Production of ethyl 3-amino-4-cyclohexylaminobenzoate

Ethyl 4-cyclohexylamino-3-nitrobenzoate (400 g) obtained in the previousstep was dissolved in ethyl acetate (1500 ml) and ethyl alcohol (500ml), and 7.5% palladium carbon (50% wet, 40 g) was added. The mixturewas hydrogenated for 7 hr at atmospheric pressure. The catalyst wasfiltered off and the filtrate was concentrated under reduced pressure.Diisopropyl ether was added to the residue and the precipitated crystalswere collected by filtration to give the title compound (289 g, yield80%).

¹H-NMR (300 MHz, CDCl₃): 7.57(1H, dd, J=8.4, 1.9 Hz), 7.41(1H, d, J=1.9Hz), 6.59(1H, d, J=8.4 Hz), 4.30(2H, q, J=7.1 Hz), 3.40-3.30(1H, m),2.18-2.02(2H, m), 1.88-1.15(8H, m), 1.35(3H, t, J=7.1 Hz)

Step 4: Production of ethyl3-[4-(3-bromophenoxy)benzoyl]amino-4-cyclohexylaminobenzoate

4-(3-Bromophenoxy)benzoic acid (74 g) was dissolved in chloroform (500ml), and oxalyl chloride (33 ml) and dimethylformamide (catalyticamount) were added. The mixture was stirred for 4 hr at roomtemperature. The reaction mixture was concentrated under reducedpressure and dissolved in dichloromethane (150 ml). The resultingsolution was added dropwise to a solution of ethyl3-amino-4-cyclohexylaminobenzoate (66 g) obtained in the previous stepin dichloromethane (500 ml) and triethylamine (71 ml), and the mixturewas stirred for 1 hr at room temperature. The reaction mixture waspoured into water and extracted with dichloromethane. The organic layerwas washed with saturated brine, dried over anhydrous magnesium sulfate,and concentrated under reduced pressure. Diethyl ether was added to theresidue for crystallization and the crystals were collected byfiltration to give the title compound (129 g, yield 95%).

¹H-NMR (300 MHz, CDCl₃): 8.00-7.78(4H, m), 7.66(1H, brs), 7.37-7.18(3H,m), 7.13-6.59(3H, m), 6.72(1H, d, J=8.7 Hz), 4.50(1H, brs), 4.29(2H, q,J=7.2 Hz), 3.36(1H, m), 2.12-1.96(2H, m), 1.83-1.56(3H, m),1.47-1.12(5H, m), 1.37(3H, t, J=7.2 Hz)

Step 5: Production of ethyl2-[4-(3-bromophenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate

Ethyl 3-[4-(3-bromophenoxy)benzoyl]amino-4-cyclohexylaminobenzoate (129g) obtained in the previous step was suspended in acetic acid (600 ml)and the resulting suspension was refluxed under heating for 3 hr. Thereaction mixture was concentrated under reduced pressure. Water wasadded to the residue and the precipitated crystals were collected byfiltration to give the title compound (124 g, yield 99%).

¹H-NMR (300 MHz, CDCl₃): 8.51(1H, d, J=1.5 Hz), 8.00(1H, dd, J=8.4, 1.5Hz), 7.67(1H, d, J=8.4 Hz), 7.63(2H, d, J=8.7 Hz), 7.35-7.21(3H, m),7.17(2H, d, J=8.7 Hz), 7.14(1H, m), 4.42(2H, q, J=7.2 Hz), 4.38(1H, m),2.43-2.22(2H, m), 2.07-1.87(4H, m), 1.80(1H, m), 1.42(3H, t, J=7.2 Hz),1.40-1.27(3H, m)

EXAMPLE 2 Production of2-[4-(3-bromophenoxy)phenyl]-1-cyclohexyl-benzimidazole-5-carboxylicacid

Ethyl2-[4-(3-bromophenoxy)phenyl]-1-cyclohexyl-benzimidazole-5-carboxylate(1.0 g) obtained in Example 1 was dissolved in tetrahydrofuran (10 ml)and ethyl alcohol (10 ml), and 4N sodium hydroxide (10 ml) was added.The mixture was refluxed under heating for 1 hr. The reaction mixturewas concentrated under reduced pressure and water was added to theresidue. The mixture was acidified with 6N hydrochloric acid and theprecipitated crystals were collected by filtration to give the titlecompound (0.9 g, yield 96%).

melting point: 255-256° C.

FAB-Ms: 491(MH+)

¹H-NMR (300 MHz, DMSO-d₆): (12.75(1H, brs), 8.24(1H, s), 7.96(1H, d,J=8.7 Hz), 7.86(1H, d, J=8.7 Hz), 7.71(2H, d, J=8.6 Hz), 7.47-7.34(3H,m), 7.24(2H, d, J=8.6 Hz), 7.20(1H, m), 4.31(1H, m), 2.38-2.18(2H, m),2.02-1.79(4H, m), 1.65(1H, m), 1.44-1.20(3H, m)

EXAMPLE 3 Production of ethyl1-cyclohexyl-2-(4-hydroxyphenyl)benzimidazole-5-carboxylate

Ethyl 3-amino-4-cyclohexylaminobenzoate (130 g) obtained in Example 1,Step 3, and methyl 4-hydroxybenzimidate hydrochloride (139 g) were addedto methyl alcohol (1500 ml), and the mixture was refluxed under heatingfor 4 hr. The reaction mixture was allowed to cool and the precipitatedcrystals were collected by filtration to give the title compound (131 g,yield 72%).

¹H-NMR (300 MHz, CDCl₃): 10.02(1H, brs), 8.21(1H, d, J=1.4 Hz), 7.93(1H,d, J=8.6 Hz), 7.83(1H, dd, J=8.6, 1.4 Hz), 7.48(2H, d, J=8.6 Hz),6.95(2H, d, J=8.6 Hz), 4.39-4.25(1H, m), 4.33(1H, q, J=7.0 Hz),2.35-2.18(2H, m), 1.98-1.79(4H, m), 1.70-1.60(1H, m), 1.46-1.19(3H, m),1.35(3H, t, J=7.0 Hz)

EXAMPLE 4 Production of ethyl2-[4-(2-bromo-5-chlorobenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate

2-Bromo-5-chlorobenzyl bromide prepared from 2-bromo-5-chlorotoluene (50g), N-bromosuccinimide and N,N′-azobisisobutyronitrile, and ethyl1-cyclohexyl-2-(4-hydroxyphenyl)benzimidazole-5-carboxylate (50 g)obtained in Example 3 were suspended in dimethylformamide (300 ml).Potassium carbonate (38 g) was added and the mixture was stirred for 1hr at 80° C. with heating. The reaction mixture was allowed to cool andthen added to a mixed solvent of water-ethyl acetate. The precipitatedcrystals were collected by filtration to give the title compound (50 g,yield 64%).

¹H-NMR (300 MHz, CDCl₃): 8.50(1H, d, J=1.4 Hz), 7.97(1H, dd, J=8.6, 1.4Hz), 7.70-7.57(5H, m), 7.20(1H, dd, J=8.4, 2.5 Hz), 7.14(2H, d, J=8.7Hz), 5.17(2H, s), 4.46-4.30(1H, m), 4.41(2H, q, J=7.1 Hz), 2.40-2.20(2H,m), 2.02-1.21(8H, m), 1.42(3H, t, J=7.1 Hz)

EXAMPLE 5 Production of ethyl2-{4-[2-(4-chlorophenyl)-5-chlorobenzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylate

Ethyl2-[4-(2-bromo-5-chlorobenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate(49 g) obtained in Example 4,4-chlorophenylboronic acid (18 g) andtetrakis-(triphenylphosphine)palladium (10 g) were suspended in1,2-dimethoxyethane (600 ml). Saturated aqueous sodium hydrogencarbonatesolution (300 ml) was added and the mixture was refluxed under heatingfor 2 hr. Chloroform was added to the reaction mixture. The organiclayer was washed successively with saturated aqueous sodiumhydrogencarbonate solution, water and saturated brine, dried overanhydrous magnesium sulfate, and concentrated under reduced pressure.The residue was purified by silica gel flash chromatography (developingsolvent, chloroform:ethyl acetate=97:3). Ethyl acetate and diisopropylether were added to the resulting oil for crystallization and theresulting crystals were collected by filtration to give the titlecompound (44 g, yield 85%).

¹H-NMR (300 MHz, CDCl₃): 8.49(1H, d, J=1.4 Hz), 7.97(1H, dd, J=8.6, 1.6Hz), 7.70-7.60(2H, m), 7.55(2H, d, J=8.7 Hz), 4.95(2H, s), 4.48-4.28(1H,m), 4.40(2H, m), 2.02-1.20(8H, m), 1.41(3H, t, J=7.1 Hz)

EXAMPLE 6 Production of2-{4-[2-(4-chlorophenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylicacid

Ethyl2-{4-[2-(4-chlorophenyl)-5-chlorobenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate(43 g) obtained in Example 5 was treated in the same manner as inExample 2 to give the title compound (33 g, yield 76%).

melting point: 243-244° C.

FAB-Ms: 571(MH+)

¹H-NMR (300 MHz, DMSO-d₆): 8.32(1H, s), 8.28(1H, d, J=8.9 Hz), 8.05(1H,d, J=8.8 Hz), 7.76-7.72(3H, m), 7.58-7.46(5H, m), 7.40(1H, d, J=8.3 Hz),7.24(2H, d, J=8.9 Hz), 5.11(2H, s), 4.36(1H, m), 2.40-2.15(2H, m),2.15-1.95(2H, m), 1.95-1.75(2H, m), 1.75-1.55(1H, m), 1.55-1.15(3H, m)

EXAMPLE 7 Production of ethyl2-[4-(2-bromo-5-methoxybenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate

Ethyl 1-cyclohexyl-2-(4-hydroxyphenyl)benzimidazole-5-carboxylateobtained in Example 3 and 2-bromo-5-methoxybenzyl bromide were treatedin the same manner as in Example 4 to give the title compound (59 g).

EXAMPLE 8 Production of ethyl2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylate

Ethyl2-[4-(2-bromo-5-methoxybenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylateobtained in Example 7 was treated in the same manner as in Example 5 togive the title compound (48 g, yield 77%).

¹H-NMR (300 MHz, CDCl₃): 8.49(1H, d, J=1.4 Hz), 7.97(1H, dd, J=8.6, 1.4Hz), 7.64(1H, d, J=8.6 Hz), 7.54(2H, d, J=8.7 Hz), 7.37(2H, d, J=8.6Hz), 7.31(2H, d, J=8.6 Hz), 7.25(1H, d, J=8.4 Hz), 7.19(1H, d, J=2.7Hz), 7.00(2H, d, J=8.7 Hz), 6.97(1H, dd, J=8.4, 2.7 Hz), 4.98(2H, s),4.41(2H, q, J=7.1 Hz), 4.42-4.29(1H, m), 3.88(3H, s), 2.40-2.20(2H, m),2.01-1.88(4H, m), 1.83-1.73(1H, m), 1.42(3H, t, J=7.1 Hz), 1.41-1.25(3H,m)

EXAMPLE 9 Production of2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylicacid

Ethyl2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate(52 g) obtained in Example 8 was treated in the same manner as inExample 2 to give the title compound (44 g, yield 89%).

melting point: 248-249° C.

FAB-Ms: 568(MH+)

¹H-NMR (300 MHz, DMSO-d₆): 8.20(1H, s), 7.88(1H, d, J=8.7 Hz), 7.85(1H,d, J=8.7 Hz), 7.57(d, 2H, J=8.6 Hz), 7.46(2H, d, J=8.6 Hz), 7.44(2H, d,J=8.6 Hz), 7.29(1H, d, J=8.5 Hz), 7.24(1H, d, J=2.6 Hz), 7.11(2H, d,J=8.6 Hz), 7.06(1H, dd, J=8.5, 2.6 Hz), 5.04(2H, s), 4.26(1H, m),3.83(3H, s), 2.38-2.29(2H, m)

EXAMPLE 10 Production of ethyl1-cyclohexyl-2-{4-[(E)-2-phenylvinyl]phenyl}-benzimidazole-5-carboxylate

Ethyl 3-amino-4-cyclohexylaminobenzoate (500 mg) obtained in Example 1,Step 3, was dissolved in methyl alcohol (6 ml) andtrans-4-stilbenecarbaldehyde (397 mg) was added under ice-cooling. Themixture was stirred overnight at room temperature. The reaction mixturewas ice-cooled and benzofuroxan (259 mg) dissolved in acetonitrile (2ml) was added. The mixture was stirred for 7 hr at 50° C. The reactionmixture was ice-cooled. After 1N sodium hydroxide was added, ethylacetate was added and the mixture was extracted. The organic layer waswashed with water and saturated brine, dried over anhydrous magnesiumsulfate, and concentrated under reduced pressure. The residue waspurified by silica gel flash chromatography (developing solvent,n-hexane:ethyl acetate=4:1) to give the title compound (540 mg, yield63%).

¹H-NMR (300 MHz, DMSO-d₆): 8.28(1H, d, J=1.4 Hz), 8.01(1H, d, J=8.7 Hz),7.90-7.80(3H, m), 7.75-7.65(4H, m), 7.50-7.25(5H, m), 4.35(2H, q, J=7.0Hz), 4.31(1H, m), 2.40-2.20(2H, m), 2.00-1.80(4H, m), 1.63(1H, m),1.40-1.20(3H, m), 1.36(3H, t, J=7.0 Hz)

EXAMPLE 11 Production of1-cyclohexyl-2-{4-[(E)-2-phenylvinyl]phenyl}-benzimidazole-5-carboxylicacid

Ethyl1-cyclohexyl-2-{4-[(E)-2-phenylvinyl]phenyl}-benzimidazole-5-carboxylate(127 mg) obtained in Example 10 was treated in the same manner as inExample 2 to give the title compound (116 mg, yield 97%).

melting point: not lower than 300° C.

FAB-Ms: 423(MH+)

¹H-NMR (300 MHz, DMSO-d₆): 8.25(1H, s), 7.96-7.29(13H, m), 4.33(1H,brt), 2.41-2.23(2H, m), 2.03-1.78(4H, m), 1.71-1.59(1H, m),1.49-1.20(3H, m)

EXAMPLE 12 Production of2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxylic acid

In the same manner as in Examples 1 and 2, the title compound (700 mg)was obtained.

FAB-Ms: 413(MH+)

¹H-NMR (300 MHz, CDCl₃): 8.60(1H, s), 8.04(1H, d, J=9.0 Hz), 7.63(2H, d,J=8.4 Hz), 7.51-7.32(6H, m), 7.14(2H, d, J=9.0 Hz), 5.16(2H, s),5.03-4.89(1H, m), 2.41-1.63(8H, m)

EXAMPLE 13 Production of2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxamide

2-(4-Benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxylic acid (700mg) obtained in Example 12 was dissolved in dimethylformamide (10 ml),and ammonium chloride (108 mg),1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (390 mg),1-hydroxybenzotriazole (275 mg) and triethylamine (0.3 ml) were added.The mixture was stirred overnight at room temperature. Water was addedto the reaction mixture and the mixture was extracted with ethylacetate. The organic layer was washed successively with saturatedaqueous sodium hydrogencarbonate, water and saturated brine, dried overanhydrous magnesium sulfate, and concentrated under reduced pressure.Ethyl acetate and diisopropyl ether were added to the residue forcrystallization and the crystals were collected by filtration to givethe title compound (571 mg, yield 81%).

melting point: 232-233° C.

FAB-Ms: 412(MH+)

¹H-NMR (300 MHz, CDCl₃): 8.23(1H, d, =1.5 Hz), 7.86(1H, dd, J=8.5, 1.5Hz), 7.65-7.30(8H, m), 7.13(2H, d, J=8.8 Hz), 5.16(2H, s), 4.93(1H,quint, J=8.8 Hz), 2.40-1.60(8H, m)

EXAMPLE 14 Production of2-(4-benzyloxyphenyl)-5-cyano-1-cyclopentylbenzimidazole

In the same manner as in Example 1, the title compound (400 mg) wasobtained.

FAB-Ms: 394(MH+)

¹H-NMR (300 MHz, CDCl₃): 8.11(1H, s), 7.68-7.30(9H, m), 7.13(2H, s),5.16(2H, s), 4.94(1H, quint, J=8.9 Hz), 2.35-1.60(8H, m)

EXAMPLE 15 Production of2-(4-benzyloxyphenyl)-1-cyclopentylbenzimidazole-5-carboxamide oxime

2-(4-Benzyloxyphenyl)-5-cyano-1-cyclopentylbenzimidazole (400 mg)obtained in Example 14 was suspended in ethyl alcohol (3 ml) and water(1.5 ml), and hydroxylamine hydrochloride (141 mg) and sodiumhydrogencarbonate (170 mg) were added. The mixture was refluxed underheating overnight. The reaction mixture was allowed to cool and theprecipitated crystals were collected by filtration to give the titlecompound (312 mg, yield 71%).

melting point: 225-226° C.

FAB-Ms: 456(MH+)

¹H-NMR (300 MHz, DMSO-d₆): 8.20(1H, s), 7.50-7.31(9H, m), 7.12(2H, d,J=8.7 Hz), 5.15(2H, s), 4.94(1H, quint, J=8.7 Hz), 3.61(3H, s), 3.40(3H,s), 2.41-1.42(8H, m)

EXAMPLE 16 Production of ethyl1-cyclohexyl-2-{4-[{4-(4-fluorophenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylate

Step 1: Production of4-(4-fluorophenyl)-5-hydroxymethyl-2-methylthiazole

Ethyl 4-(4-fluorophenyl)-2-methyl-5-thiazolecarboxylate (59 g) preparedby a known method (Chem. Pharm. Bull., 43(6), 947, 1995) was dissolvedin tetrahydrofuran (700 ml). Lithium aluminum hydride (13 g) was addedunder ice-cooling and the mixture was stirred for 30 min. Water (13 ml),15% sodium hydroxide (13 ml) and water (39 ml) were added successivelyto the reaction mixture, and the precipitated insoluble materials werefiltered off. The filtrate was concentrated under reduced pressure togive the title compound (37 g, yield 71%).

¹H-NMR (300 MHz, CDCl₃): 7.60(2H, dd, J=8.7, 6.6 Hz), 7.11(2H, t, J=8.7Hz), 4.80(2H, s), 2.70(3H, s)

Step 2: Production of 5-chloromethyl-4-(4-fluorophenyl)-2-methylthiazole

4-(4-Fluorophenyl)-5-hydroxymethyl-2-methylthiazole (37 g) obtained inthe previous step was dissolved in chloroform (500 ml), and thionylchloride (24 ml) and pyridine (2 ml) were added. The mixture was stirredfor 3 hr at room temperature. The reaction mixture was poured intoice-cold water. The mixture was extracted with chloroform, and washedwith water and saturated brine. The organic layer was dried over sodiumsulfate, and concentrated under reduced pressure to give the titlecompound (29 g, yield 76%).

¹H-NMR (300 MHz, CDCl₃): 7.67(2H, dd, J=8.8, 5.4 Hz), 7.16(2H, t, J=8.7Hz), 4.79(2H, s), 2.73(3H, s)

Step 3: Production of ethyl1-cyclohexyl-2-{4-[{-4-(4-fluorophenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylate

5-Chloromethyl-4-(4-fluorophenyl)-2-methylthiazole (28 g) obtained inthe previous step and ethyl1-cyclohexyl-2-(4-hydroxyphenyl)benzimidazole-5-carboxylate (36 g)obtained in Example 3 were treated in the same manner as in Example 4 togive the title compound (61 g, yield 100%).

APCI-Ms: 570(MH+)

¹H-NMR (300 MHz, DMSO-d₆): 8.25(1H, d, J=1.5 Hz), 7.97(1H, d, J=8.7 Hz),7.86(1H, dd, J=8.6, 1.6 Hz), 7.74(2H, dd, J=8.8, 5.5 Hz), 7.62(2H, d,J=8.7 Hz), 7.33(2H, t, J=8.9 Hz), 7.22(2H, t, J=8.9 Hz), 5.41(2H, s),4.34(2H, q, J=7.1 Hz), 4.31(1H, m), 2.71(3H, s), 2.40-2.15(2H, m),2.05-1.75(4H, m), 1.55-1.15(3H, m), 1.36(3H, t, J=7.1 Hz)

EXAMPLE 17 Production of1-cyclohexyl-2-{4-[{4-(4-fluorophenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylicacid

Ethyl1-cyclohexyl-2-{4-[{4-(4-fluorophenyl)-2-methyl-5-thiazolyl}methoxy]phenyl}benzimidazole-5-carboxylate(60 g) obtained in Example 16 was treated in the same manner as inExample 2 to give the title compound (39 g, yield 69%).

melting point: 196-198° C.

FAB-Ms: 542(MH+)

¹H-NMR (300 MHz, DMSO-d₆): 13.1(1H, brs), 8.34(1H, s), 8.29(1H, d, J=8.8Hz), 8.06(1H, d, J=8.7 Hz), 7.80-7.72(4H, m), 7.36-7.31(4H, m), 5.46(2H,s), 4.38(1H, m), 2.72(3H, s), 2.45-2.15(2H, m), 2.15-1.95(2H, m),1.95-1.75(2H, m), 1.75-1.55(1H, m), 1.55-1.20(3H, m)

EXAMPLE 18 Production of ethyl1-cyclohexyl-2-(2-fluoro-4-hydroxyphenyl)-benzimidazole-5-carboxylate

In the same manner as in Example 3, the title compound (50 g) wasobtained.

EXAMPLE 19 Production of ethyl2-{4-[bis(3-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate

Step 1: Production of 3,3′-difluorobenzhydrol

To a stirred solution of magnesium strip (35.4 g) in THF (200 ml),iodine strip was added and the mixture was heated with stirring undernitrogen stream until most of color of iodine was disappeared. Asolution of 3-fluoro-bromobenzene (250.0 g) in THF (1000 ml) was addeddropwise over 2.5 hr while the temperature of the solution wasmaintained at 60° C. After the completion of the addition of thesolution, the resulting mixture was refluxed for 1 hr with heating. Theresulting Grignard solution was ice-cooled and a solution of ethylformate (63.2 g) in THF (200 ml) was added dropwise over 1 hr. After astirring of the reaction solution for an additional 30 min, saturatedaqueous ammonium chloride solution (700 ml) was added dropwise withice-cooling and water (300 ml) was added. The mixture was stirred for 10min. The organic layer and water layer were separated. Water layer wasextracted with ethyl acetate, and the combined organic layer was washedwith 2N hydrochloric acid, saturated aqueous sodium hydrogencarbonateand saturated brine. The organic layer was dried over anhydrousmagnesium sulfate, filtered, and the solvent was evaporated off underreduced pressure to give the title compound (156.2 g, yield 99%).

¹H-NMR (300 MHz, CDCl₃): 7.31(2H, td, J=7.9, 5.8 Hz), 7.15-7.80(4H, m),6.97-6.94(2H, m), 5.82(1H, d, J=3.3 Hz), 2.30(1H, d, J=3.3 Hz)

Step 2: Production of 3,3′-difluorobenzhydryl chloride

To a solution of 3,3′-difluorobenzhydrol (150.0 g) obtained in theprevious step in toluene (400 ml), pyridine (539 mg) was added at roomtemperature. To the solution, thionyl chloride (89.1 g) was addeddropwise over 1 hr at room temperature and the resulting solution wasstirred for an additional 2 hr. The solution was heated so that thetemperature of the solution was at 40° C., and then stirred for anadditional 1.5 hr. Thionyl chloride (8.1 g) was added again and themixture was stirred for 30 min. To the reaction mixture, water wasadded. The organic layer was separated, and washed with water, saturatedaqueous sodium hydrogencarbonate and saturated brine. The organic layerwas dried over anhydrous magnesium sulfate, filtered, the solvent wasevaporated off under reduced pressure to give the title compound (158.2g, yield 97%).

¹H-NMR (300 MHz, CDCl₃): 7.32(2H, td, J=8.0, 5.9 Hz), 7.18-7.10(4H, m),7.01(2H, tdd, J=8.2, 2.5, 1.2 Hz), 6.05(1H, s)

Step 3: Production of ethyl2-{4-(bis(3-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate

Ethyl1-cyclohexyl-2-(2-fluoro-4-hydroxyphenyl)-benzimidazole-5-carboxylate(50 g) obtained in Example 18 and 3,3′-difluorobenzhydryl chloride (34g) obtained in the previous step were treated in the same manner as inExample 4 to give the title compound (76 g, yield 99%).

FAB-Ms: 585(MH+)

¹H-NMR (300 MHz, DMSO-d₆): 8.24(1H, d, J=1.4 Hz), 7.98(1H, d, J=8.7 Hz),7.88(1H, d, J=8.7 Hz), 7.56(1H, t, J=8.6 Hz), 7.50-7.40(6H, m), 6.82(1H,s), 4.34(2H, q, J=7.1 Hz), 3.95(1H, m), 2.20-2.10(2H, m), 1.90-1.80(4H,m), 1.6(1H, m), 1.35(3H, t, J=7.2 Hz), 1.30-1.20(3H, mz)

EXAMPLE 20 Production of2-{4-(bis[3-fluorophenyl]methoxy)-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylicacid

Ethyl2-{4-[bis(3-fluorophenyl)methoxy]-2-fluorophenyl}-1-cyclohexylbenzimidazole-5-carboxylate(75 g) obtained in Example 19 was treated in the same manner as inExample 2 to give the title compound (48 g, yield 62%).

melting point: 242-243° C.

FAB-Ms: 557(MH+)

¹H-NMR (300 MHz, DMSO-d₆): 8.29(1H, s), 8.16(1H, d, J=8.8 Hz), 7.99(1H,d, J=8.7 Hz), 7.66(1H, t, J=8.7 Hz), 7.51-7.40(6H, m), 7.30(1H, d,J=12.1 Hz), 7.20-7.14(3H, m), 6.88(1H, s), 4.07(1H, m), 2.40-2.10(2H,m), 2.00-1.75(4H, m), 1.70-1.55(1H, m), 1.50-1.15(3H, m)

EXAMPLE 21 Production of ethyl1-cyclopentyl-2-(4-nitrophenyl)benzimidazole-5-carboxylate

In the same manner as in Example 1, the title compound (12 g) wasobtained.

EXAMPLE 22 Production of ethyl2-(4-aminophenyl)-1-cyclopentylbenzimidazole-5-carboxylate

Ethyl 1-cyclopentyl-2-(4-nitrophenyl)benzimidazole-5-carboxylate (12 g)obtained in Example 21 was dissolved in tetrahydrofuran (200 ml) andethyl alcohol (50 ml), 7.5% palladium carbon (50% wet, 1 g) was added.The mixture was hydrogenated for 1 hr at atmospheric pressure. Thecatalyst was filtered off and the filtrate was concentrated underreduced pressure. Tetrahydrofuran was added to the residue to allowcrystallization and the crystals were collected by filtration to givethe title compound (11 g, yield 98%).

¹H-NMR (300 MHz, CDCl₃): 8.49(1H, d, J=1.3 Hz), 7.95(1H, dd, J=8.5, 1.3Hz), 7.50-7.40(3H, m), 6.79(2H, d, J=4.6 Hz), 4.97(1H, quint, J=8.9 Hz),4.40(2H, q, J=7.1 Hz), 3.74(2H, brs), 2.40-1.60(8H, m), 1.41(3H, t,J=7.1 Hz)

EXAMPLE 23 Production of ethyl2-(4-benzoylaminophenyl)-1-cyclopentylbenzimidazole-5-carboxylate

Ethyl 1-cyclopentyl-2-(4-aminophenyl)benzimidazole-5-carboxylate (300mg) obtained in Example 22 was dissolved in pyridine (3 ml) andchloroform (3 ml), and benzoyl chloride (127 mg) was added. The mixturewas stirred for 30 min at room temperature. The reaction mixture wasconcentrated under reduced pressure and water was added to the residueto allow crystallization. The crystals were collected by filtration togive the title compound (403 mg, yield 100%).

¹H-NMR (300 MHz, CDCl₃): 8.58(1H, s), 8.00(1H, d, J=9.0 Hz), 7.84(2H, d,J=7.5 Hz), 7.60-7.40(6H, m), 7.14(2H, d, J=7.5 Hz), 4.84(1H, quint,J=8.7 Hz), 4.41(2H, q, J=7.5 Hz), 2.20-1.30(8H, m), 1.41(3H, t, J=7.5Hz)

EXAMPLE 24 Production of2-(4-benzoylaminophenyl)-1-cyclopentylbenzimidazole-5-carboxylic acid

Ethyl 2-(4-benzoylaminophenyl)-1-cyclopentylbenzimidazole-5-carboxylate(200 mg) obtained in Example 23 was treated in the same manner as inExample 2 to give the title compound (131 mg, yield 70%).

melting point: not lower than 300° C.

FAB-Ms: 426(MH+)

¹H-NMR (300 MHz, DMSO-d₆): 10.75(1H, s), 8.35(1H, s), 8.15 and 7.85(4H,ABq, J=8.9 Hz), 8.10-7.98(4H, m), 7.70-7.55(3H, m), 5.02(1H, quint,J=8.7 Hz), 2.36-2.15(4H, m), 2.14-1.95(2H, m), 1.80-1.62(2H, m)

EXAMPLE 25 Production of ethyl2-{4-[3-(3-chlorophenyl)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate

Ethyl2-[4-(3-bromophenoxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate (65g) obtained in Example 1 and 3-chlorophenylboronic acid (23 g) weretreated in the same manner as in Example 5 to give the title compound(59 g, yield 85%).

¹H-NMR (300 MHz, CDCl₃): 8.51(1H, d, J=1.8 Hz), 7.99(1H, dd, J=8.7, 1.8Hz), 7.71-7.55(4H, m), 7.51-7.43(2H, m), 7.43-7.27(4H, m), 7.19(1H, d,J=8.4 Hz), 7.12(1H, m), 4.41(2H, q, J=7.2 Hz), 4.39(1H, m),2.42-2.22(2H, m), 2.03-1.87(4H, m), 1.79(1H, m), 1.42(3H, t, J=7.2 Hz),1.39-1.29(3H, m)

EXAMPLE 26 Production of2-{4-[3-(3-chlorophenyl)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylicacid

Ethyl2-{4-[3-(3-chlorophenyl)phenoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate(59 g) obtained in Example 25 was treated in the same manner as inExample 2 to give the title compound (43 g, yield 76%).

melting point: 253-254° C.

FAB-Ms: 523(MH+)

¹H-NMR (300 MHz, DMSO-d₆): 12.82(1H, brs), 8.24(1H, d, J=1.3 Hz),7.98(1H, d, J=8.7 Hz), 7.89(1H, dd, J=8.7, 1.3 Hz), 7.78(1H, s),7.72(2H, d, J=9.7 Hz), 7.70(1H, m), 7.64-7.42(5H, m), 7.25(2H, d, J=8.7Hz), 7.20(1H, m), 4.33(1H, m), 2.39-2.17(2H, m), 2.00-1.76(4H, m),1.65(1H, m), 1.50-1.22(3H, m)

EXAMPLE 27 Production of ethyl2-[4-(3-acetoxyphenyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate

In the same manner as in Example 1, the title compound (87 g) wasobtained.

EXAMPLE 28 Production of ethyl1-cyclohexyl-2-[4-(3-hydroxyphenyloxy)-phenyl]benzimidazole-5-carboxylate

Ethyl2-[4-(3-acetoxyphenyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate(87 g) obtained in Example 27 was dissolved in methyl alcohol (250 ml)and tetrahydrofuran (250 ml), and potassium carbonate (31 g) was added.The mixture was stirred for 30 min at room temperature. The insolublematerials were filtered off and the filtrate was concentrated underreduced pressure. Water was added to the residue and the mixture wasneutralized with 2N hydrochloric acid. The precipitated crystals werecollected by filtration to give the title compound (78 g, yield 97%).

¹H-NMR (300 MHz, DMSO-d₆): 9.71(1H, s), 7.98(1H, d, J=8.7 Hz), 7.87(1H,d, J=8.7 Hz), 7.68(2H, d, J=8.6 Hz), 7.24(1H, t, J=8.1 Hz), 7.18(2H, d,J=8.6 Hz), 6.63(1H, d, J=8.1 Hz), 6.57(1H, d, J=8.1 Hz), 6.51(1H, s),4.38-4.23(1H, m), 4.35(2H, q, J=6.9 Hz), 2.36-2.18(2H, m), 1.99-1.78(4H,m), 1.71-1.59(1H, m), 1.45-1.20(3H, m), 1.36(3H, t, J=6.9 Hz)

EXAMPLE 29 Production of ethyl1-cyclohexyl-2-{4-[3-(4-pyridylmethoxy)-phenyloxy]phenyl}benzimidazole-5-carboxylate

Ethyl1-cyclohexyl-2-[4-(3-hydroxyphenyloxy)phenyl]-benzimidazole-5-carboxylate(78 g) obtained in Example 28 was suspended in dimethylformamide (800ml), and sodium hydride (60% oil, 14 g) was added under ice-cooling. Themixture was stirred for 1 hr at room temperature. After the reactionmixture was ice-cooled, 4-chloromethylpyridine hydrochloride (29 g) wasadded and the mixture was stirred for 30 min. The mixture was thenstirred overnight at room temperature. Water was added to the reactionmixture and the precipitated crystals were collected by filtration. Theresulting crystals were recrystallized from ethyl alcohol to give thetitle compound (77 g, yield 82%).

¹H-NMR (300 MHz, CDCl₃): 8.63(2H, d, J=6.0 Hz), 8.51(1H, s), 7.99(1H, d,J=8.7 Hz), 7.66(2H, d, J=8.7 Hz), 7.62(2H, d, J=8.7 Hz), 7.36(2H, d,J=8.7 Hz), 7.31(1H, t, J=8.2 Hz), 7.26(1H, s), 7.16(2H, d, J=8.7 Hz),6.79-6.70(3H, m), 5.09(2H, s), 4.47-4.31(1H, m), 4.42(2H, q, J=7.0 Hz),2.42-2.22(2H, m), 2.04-1.71(5H, m), 1.45-1.25(3H, m), 1.42(3H, t, J=7.0Hz)

EXAMPLE 30 Production of1-cyclohexyl-2-{4-[3-(4-pyridylmethoxy)phenyloxy]-phenyl}benzimidazole-5-carboxylicacid

Ethyl1-cyclohexyl-2-{4-[3-(4-pyridylmethoxy)phenyloxy]-phenyl}benzimidazole-5-carboxylate(60 g) obtained in Example 29 was treated in the same manner as inExample 2 to give the title compound (54 g, yield 75%).

melting point: 235-237° C.

FAB-Ms: 520(MH+)

¹H-NMR (300 MHz, DMSO-d₆): 8.58(2H, d, J=6.0 Hz), 8.23(1H, s), 7.96 and7.86(2H, ABq, J=8.7 Hz), 7.68 and 7.17(4H, A′B′q, J=8.7 Hz), 7.44(2H, d,J=8.7 Hz), 7.39(1H, t, J=8.3 Hz), 6.90(1H, d, J=8.1 Hz), 6.84(1H, s),6.75(1H, d, J=8.1 Hz), 5.22(2H, s), 4.40-4.22(1H, m), 2.40-2.19(2H, m),2.00-1.80(4H, m)

EXAMPLE 241 Production of methyl2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate

Step 1: Production of 2-bromo-5-methoxybenzaldehyde

3-Methoxybenzaldehyde (15 g) was dissolved in acetic acid (75 ml), and asolution of bromine (5.7 ml) dissolved in acetic acid (15 ml) was addeddropwise. The mixture was stirred overnight at room temperature andwater (150 ml) was added to the reaction mixture. The precipitatedcrystals were collected by filtration, washed with water and dried underreduced pressure to give the title compound (21 g, yield 88%).

¹H-NMR (300 MHz, CDCl₃): 10.31(1H, s), 7.52(1H, d, J=8.8 Hz), 7.41(1H,d, J=3.3 Hz), 7.03(1H, dd, J=8.8, 3.3 Hz), 3.48(3H, s)

Step 2: Production of 2-(4-chlorophenyl)-5-methoxybenzaldehyde

2-Bromo-5-methoxybenzaldehyde (10 g) obtained in the previous step wastreated in the same method as in Example 5 to give the title compound(11 g, yield 96%).

¹H-NMR (300 MHz, CDCl₃): 9.92(1H, s), 7.50(1H, d, J=2.6 Hz),7.48-7.14(6H, m), 3.90(3H, s)

Step 3: Production of 2-(4-chlorophenyl)-5-methoxybenzyl alcohol

2-(4-Chlorophenyl)-5-methoxybenzaldehyde (10 g) obtained in the previousstep was dissolved in tetrahydrofuran (30 ml). The solution was addeddropwise to a suspension of sodium borohydride (620 mg) in isopropylalcohol (50 ml) and the mixture was stirred for 1 hr. The solvent wasevaporated under reduced pressure and water was added to the residue.The precipitated crystals were collected by filtration and dried underreduced pressure. The resulting crystals were recrystallized from amixture of methanol and water to give the title compound (9.2 g, yield91%).

¹H-NMR (300 MHz, CDCl₃): 7.37(2H, d, J=8.6 Hz), 7.27(2H, d, J=8.6 Hz),7.17(1H, d, J=8.6 Hz), 7.11(1H, d, J=2.6 Hz), 6.89(1H, dd, J=8.6, 2.6Hz), 4.57(2H, s), 3.86(3H, s)

Step 4: Production of 2-(4-chlorophenyl)-5-methoxybenzyl chloride

2-(4-Chlorophenyl)-5-methoxybenzyl alcohol (20 g) obtained in theprevious step was dissolved in ethyl acetate (100 ml) and pyridine (0.5ml), and thionyl chloride (11 ml) was added dropwise. The mixture wasstirred for 1 hr. Water was added to the reaction mixture and themixture was extracted with ethyl acetate. The organic layer was washedwith water, saturated aqueous sodium hydrogencarbonate, water andsaturated brine, dried over anhydrous magnesium sulfate, andconcentrated under reduced pressure. Isopropyl alcohol was added to theresidue to allow crystallization. The resulting crystals were collectedby filtration and dried under reduced pressure to give the titlecompound (16 g, yield 74%).

¹H-NMR (300 MHz, CDCl₃): 7.43-7.29(4H, m), 7.17(1H, d, J=8.6 Hz),7.05(1H, d, J=2.6 Hz), 6.96-6.89(1H, m), 4.46(2H, s), 3.86(3H, s)

Step 5: Production of methyl2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate

2-(4-Chlorophenyl)-5-methoxybenzyl chloride (4.0 g) obtained in theprevious step and methyl1-cyclohexyl-2-(4-hydroxyphenyl)-benzimidazole-5-carboxylate (5.0 g)obtained in the same manner as in Example 3 were treated in the samemanner as in Example 4 to give the title compound (6.0 g, yield 72%).

¹H-NMR (300 MHz, CDCl₃): 8.48(1H, s), 8.00-7.93(1H, m), 7.68-7.62(1H,m), 7.54(2H, d, J=9.0 Hz), 7.41-7.16(6H, m), 7.04-6.93(3H, m), 4.97(2H,s), 4.36(1H, m), 3.94(3H, s), 3.87(3H, s), 2.39-2.21(2H, m),2.02-1.88(4H, m), 1.85-1.45(4H, m)

EXAMPLE 242 Production of2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylicacid hydrochloride

Methyl2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate(5.0 g) obtained in Example 241 was treated in the same manner as inExample 2 to give the title compound (5.1 g, yield 98%).

APCI-Ms: 568(MH+)

¹H-NMR (300 MHz, DMSO-d₆): 8.30(1H, d, J=1.4 Hz), 8.24(1H, d, J=8.7 Hz),8.03(1H, d, J=8.7 Hz), 7.72(2H, d, J=8.7 Hz), 7.51-7.39(4H, m),7.34-7.18(4H, m), 7.11-7.03(1H, m), 5.08(2H, s), 4.35(1H, m), 3.83(3H,m), 2.40-2.18(2H, m), 2.10-1.96(2H, m), 1.93-1.78(2Hm), 1.72-1.18(4H, m)

EXAMPLE 243 Production of ethyl2-{4-[3-(4-chlorophenyl)pyridin-2-ylmethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate

Step 1: Production of methyl 3-hydroxypicolinate

3-Hydroxypicolinic acid (1.0 g) was suspended in methanol (10 ml) andconcentrated sulfuric acid (1.0 ml) was added. The mixture was refluxedunder heating for 5 hr. The reaction mixture was ice-cooled, neutralizedwith saturated aqueous sodium hydrogencarbonate, and extracted withchloroform. The organic layer was washed with water and saturated brine,and dried over anhydrous magnesium sulfate. The solvent was evaporatedunder reduced pressure to give the title compound (711 mg, yield 64%).

¹H-NMR (300 MHz, CDCl₃): 10.63(1H, s), 8.28(1H, dd, J=3.7, 1.8 Hz),7.47-7.35(2H, m), 4.06(3H, s)

Step 2: Production of methyl3-(trifluoromethylsulfonyloxy)-pyridine-2-carboxylate

Methyl 3-hydroxypicolinate (710 mg) obtained in the previous step andtriethylamine (0.77 ml) were dissolved in dichloromethane (7 ml), andtrifluoromethanesulfonic anhydride (0.86 ml) was added underice-cooling. The reaction mixture was allowed to warm to roomtemperature and the mixture was stirred for 2 hr. Water was added to thereaction mixture and the mixture was extracted with ethyl acetate. Theorganic layer was washed with saturated brine and dried over anhydrousmagnesium sulfate. The solvent was evaporated under reduced pressure togive the title compound (1.2 g, yield 90%).

¹H-NMR (300 MHz, CDCl₃): 8.80-8.73(1H, m), 7.75-7.70(1H, m), 7.63(1H,dd, J=8.2, 4.5 Hz), 4.05(3H, s)

Step 3: Production of methyl 3-(4-chlorophenyl)pyridine-2-carboxylate

Methyl 3-(trifluoromethylsulfonyloxy)pyridine-2-carboxylate (1.2 g)obtained in the previous step was treated in the same manner as inExample 5 to give the title compound (728 mg, yield 69%).

¹H-NMR (300 MHz, CDCl₃): 8.73-8.66(1H, m), 7.77-7.68(1H, m), 7.49(1H,dd, J=7.8, 4.5 Hz), 7.46-7.37(2H, m), 7.32-7.23(2H, m), 3.80(3H, s)

Step 4: Production of [3-(4-chlorophenyl)pyridin-2-yl]methanol

Methyl 3-(4-chlorophenyl)pyridine-2-carboxylate (720 mg) obtained in theprevious step was dissolved in tetrahydrofuran (10 ml) and the solutionwas ice-cooled. Lithium aluminum hydride (160 mg) was added to thesolution and the mixture was stirred for 1 hr. To the reaction mixturewere added successively water (1.6 ml), 15% sodium hydroxide (1.6 ml)and water (4.8 ml). The insoluble materials were filtered off and thefiltrate was concentrated under reduced pressure. The residue waspurified by silica gel flash chromatography (developing solvent,n-hexane:ethyl acetate=1:1) to give the title compound (208 mg, yield32%).

¹H-NMR (300 MHz, CDCl₃): 8.60(1H, dd, J=4.8, 1.5 Hz), 7.60-7.55(1H, m),7.40-7.48(2H, m), 7.29-7.36(1H, m), 7.27-7.20(3H, m), 4.63(2H, s)

Step 5: Production of ethyl2-{4-[3-(4-chlorophenyl)pyridin-2-ylmethoxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate

[3-(4-Chlorophenyl)pyridin-2-yl]methanol (200 mg) obtained in theprevious step was dissolved in chloroform (3 ml), and thionyl chloride(0.13 ml) and pyridine (catalytic amount) were added. The mixture wasstirred for 1 hr at room temperature and concentrated under reducedpressure. The residue was dissolved in dimethylformamide (3 ml), andethyl 1-cyclohexyl-2-(4-hydroxyphenyl)benzimidazole-5-carboxylate (232mg) obtained in the same manner as in Example 3 and potassium carbonate(250 mg) were added. The mixture was stirred for 3 hr with heating at80° C. The reaction mixture was then allowed to cool. Water was addedand the mixture was extracted with ethyl acetate. The organic layer waswashed with water and saturated brine, dried over anhydrous magnesiumsulfate and concentrated under reduced pressure. The residue waspurified by silica gel flash chromatography (developing solvent,n-hexane:ethyl acetate=1:2) to give the title compound (246 mg, yield68%).

¹H-NMR (300 MHz, CDCl₃): 8.71(1H, dd, J=4.7, 1.4 Hz), 8.49(1H, d, J=2.1Hz), 7.96(1H, d, J=10.2 Hz), 7.71-7.62(2H, m), 7.53(2H, d, J=8.7 Hz),7.45-7.34(5H, m), 7.04(2H, d, J=8.7 Hz), 5.14(2H, s), 4.48-4.29(3H, m),2.38-2.19(2H, m), 2.02-1.22(11H, m)

EXAMPLE 244 Production of methyl2-[4-(2-bromo-5-tert-butoxycarbonyl-benzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate

Step 1: Production of tert-butyl 4-bromo-3-methylbenzoate

4-Bromo-3-methylbenzoic acid (25 g) was suspended in dichloromethane(200 ml), and oxalyl chloride (12 ml) and dimethylformamide (catalyticamount) were added. The mixture was stirred for 2 hr at room temperatureand the solvent was evaporated under reduced pressure. The residue wasdissolved in tetrahydrofuran (200 ml) and the solution was ice-cooled.To the solution was added dropwise a solution of potassium tert-butoxidedissolved in tetrahydrofuran (150 ml) and the mixture was stirred for 30min. Water was added to the reaction mixture and the mixture wasextracted with ethyl acetate. The organic layer was washed with waterand saturated brine, and dried over anhydrous magnesium sulfate. Thesolvent was evaporated under reduced pressure to give the title compound(27 g, yield 85%).

¹H-NMR (300 MHz, CDCl₃): 7.83(1H, d, J=2.2 Hz), 7.67-7.53(2H, m),2.43(3H, s), 1.58(9H, s)

Step 2: Production of methyl2-[4-(2-bromo-5-tert-butoxycarbonylbenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate

tert-Butyl 4-bromo-3-methylbenzoate (7.0 g) obtained in the previousstep and methyl1-cyclohexyl-2-(4-hydroxyphenyl)-benzimidazole-5-carboxylate (6.3 g)obtained in the same manner as in Example 3 were treated in the samemanner as in Example 4 to give the title compound (8.8 g, yield 77%).

¹H-NMR (300 MHz, CDCl₃): 8.49(1H, d, J=1.5 Hz), 8.21(1H, d, J=2.1 Hz),7.97(1H, d, J=10.2 Hz), 7.82(1H, d, J=10.2 Hz), 7.71-7.58(4H, m),7.16(2H, d, J=8.7 Hz), 5.23(2H, s), 4.38(1H, m), 3.95(3H, s),2.40-2.23(2H, m), 2.04-1.90(4H, m), 1.84-1.73(1H, m), 1.59(9H, s),1.44-1.27(3H, m)

EXAMPLE 245 Production of methyl2-{4-[5-tert-butoxycarbonyl-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate

Methyl2-[4-(2-bromo-5-tert-butoxycarbonylbenzyloxy)phenyl]-1-cyclohexylbenzimidazole-5-carboxylate(4.5 g) obtained in Example 244 was treated in the same manner as inExample 5 to give the title compound (3.6 g, yield 76%).

¹H-NMR (300 MHz, CDCl₃): 8.48(1H, s), 8.27(1H, d, J=1.8 Hz), 8.04(1H,dd, J=7.9, 1.5 Hz), 7.96(1H, dd, J=7.0, 1.5 Hz), 7.65(1H, d, J=8.6 Hz),7.55(2H, d, J=8.6 Hz), 7.43-7.32(5H, m), 7.01(2H, d, J=8.6 Hz), 4.99(2H,s), 4.43-4.29(1H, m), 3.95(3H, s), 2.41-2.21(2H, m), 2.02-1.89(4H, m),1.82-1.73(1H, m), 1.62(9H, s), 1.46-1.28(3H, m)

EXAMPLE 246 Production of methyl2-{4-[5-carboxy-2-(4-chlorophenyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylatehydrochloride

Methyl2-{4-[5-tert-butoxycarbonyl-2-(4-chlorophenyl)-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate(3.5 g) obtained in Example 245 was dissolved in dichloromethane (35ml), and trifluoroacetic acid (35 ml) was added. The mixture was stirredfor 1 hr at room temperature and the reaction mixture was concentratedunder reduced pressure. The residue was dissolved in ethyl acetate, and4N hydrochloric acid-ethyl acetate was added. The precipitated crystalswere collected by filtration and dried under reduced pressure to givethe title compound (3.3 g, yield 97%).

¹H-NMR (300 MHz, DMSO-d₆): 8.33(1H, d, J=1.5 Hz), 8.29(1H, s), 8.24(1H,d, J=1.8 Hz), 8.09-8.00(2H, m), 7.74(2H, d, J=8.6 Hz), 7.61-7.44(5H, m),7.24(2H, d, J=8.6 Hz), 5.19(2H, s), 4.36(1H, m), 3.93(3H, s),2.37-1.21(10H, m)

EXAMPLE 247 Production of methyl2-{4-[2-(4-chlorophenyl)-5-methylcarbamoyl-benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylate

Methyl2-{4-[5-carboxy-2-(4-chlorophenyl)benzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylatehydrochloride (400 mg) obtained in Example 246 was suspended indichloromethane (5 ml), and oxalyl chloride (0.08 ml) anddimethylformamide (catalytic amount) were added. The mixture was stirredfor 2 hr at room temperature. The reaction mixture was concentratedunder reduced pressure and the residue was dissolved in dichloromethane(5 ml). The resulting solution was added dropwise to a mixed solution of40% aqueous methylamine solution (5 ml) and tetrahydrofuran (5 ml) underice-cooling. The reaction mixture was stirred for 1 hr and concentratedunder reduced pressure. Water was added to the residue and the mixturewas extracted with ethyl acetate. The organic layer was washed withwater, saturated aqueous sodium hydrogencarbonate and saturated brine,and dried over anhydrous magnesium sulfate. The solvent was evaporatedunder reduced pressure and the residue was crystallized from ethylacetate and diisopropyl ether. The crystals were collected by filtrationand dried under reduced pressure to give the title compound (335 mg,yield 86%).

¹H-NMR (300 MHz, CDCl₃): 8.47(1H, s), 8.06(1H, d, J=1.8 Hz), 7.96(1H,dd, J=8.6, 1.5 Hz), 7.82(1H, dd, J=8.2, 2.2 Hz), 7.64(1H, d, J=8.6 Hz),7.54(2H, d, J=9.0 Hz), 7.44-7.31(5H, m), 6.99(2H, d, J=9.0 Hz),6.35-6.26(1H, m), 5.00(2H, s), 4.35(1H, m), 3.95(3H, s), 3.05(3H, d,J=4.8 Hz), 2.40-1.24(10H, m)

EXAMPLE 248 Production of2-{4-[2-(4-chlorophenyl)-5-methylcarbamoylbenzyloxy]phenyl}-1-cyclohexylbenzimidazole-5-carboxylatehydrochloride

Methyl2-{4-[2-(4-chlorophenyl)-5-methylcarbamoylbenzyloxy]-phenyl}-1-cyclohexylbenzimidazole-5-carboxylate(150 mg) obtained in Example 247 and tetrahydrofuran (2 ml) were treatedin the same manner as in Example 2 to give the title compound (141 mg,yield 90%).

APCI-Ms: 594(MH+)

¹H-NMR (300 MHz, DMSO-d₆): 8.65-8.58(1H, m), 8.27(1H, d, J=1.5 Hz),8.21(1H, d, J=8.2 Hz), 8.15(1H, d, J=1.5 Hz), 8.05-7.90(2H, m), 7.70(2H,d, J=8.6 Hz), 7.56-7.43(5H, m), 7.21(2H, d, J=8.6 Hz), 5.14(2H, s),4.34(1H, m), 2.81(3H, d, J=4.5 Hz), 2.39-1.19(10H, m)

EXAMPLE 336 Production of methyl2-[4-(2-bromo-5-nitrobenzyloxy)-2-fluorophenyl]-1-cyclohexylbenzimidazble-5-carboxylate

Commercially available 2-bromo-5-nitrotoluene was dissolved in carbontetrachloride (30 ml), and N-bromosuccinimide (2.9 g) andN,N′-azobisisobutyronitrile (228 mg) were added, which was followed byrefluxing under heating overnight. The reaction mixture was allowed tocool, water was added and the mixture was extracted with chloroform. Theorganic layer was dried over magnesium sulfate and concentrated underreduced pressure. The residue was dissolved in dimethylformamide (30 ml)and methyl2-(2-fluoro-4-hydroxyphenyl)-1-cyclohexylbenzimidazole-5-carboxylate(3.8 g) obtained in the same manner as in Example 3 and potassiumcarbonate (3.8 g) were added, which was followed by stirring at 80° C.for 1 hr. The reaction mixture was allowed to cool, water was added andthe mixture was extracted with ethyl acetate. The organic layer waswashed with water and saturated brine, dried over anhydrous magnesiumsulfate and concentrated under reduced pressure. The residue waspurified by silica gel flash chromatography (n-hexane:ethyl acetate=1:1)to give the title compound (3.7 g, yield 61%).

¹H-NMR (300 MHz, CDCl₃): 8.55-8.45 (2H, m), 8.15-8.05 (1H, m), 7.99(1H,dd, J=8.6 Hz, 1.5 Hz), 7.70-7.55(2H, m), 7.05-6.85(2H, m), 5.24(2H, s),4.06(1H, m), 3.95(3H, s), 2.35-2.15(2H, m), 2.05-1.85(4H, m),1.80-1.70(1H, m), 1.45-1.20(3H, m)

EXAMPLE 337 Production of methyl2-[4-{2-(4-chlorophenyl)-5-nitrobenzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate

Methyl2-[4-(2-bromo-5-nitrobenzyloxy)-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate(2.0 g) obtained in Example 336, 4-chlorophenylboronic acid (590 mg) andtetrakis(triphenylphosphine)palladium (396 mg) were suspended indimethoxyethane (40 ml), and saturated aqueous sodium hydrogencarbonatesolution (20 ml) was added, which was followed by refluxing underheating for 1 hr. The reaction mixture was allowed to cool, water wasadded and the mixture was extracted with chloroform. The organic layerwas dried over anhydrous magnesium sulfate and concentrated underreduced pressure. The residue was purified by silica gel flashchromatography (n-hexane:ethyl acatate=2:1) to give the title compound(1.9 g, yield 90%).

¹H-NMR (300 MHz, CDCl₃): 8.55(1H, d, J=2.3 Hz), 8.49(1H, d, J=1.4 Hz),8.29(1H, dd, J=8.4 Hz, 2.3 Hz), 7.98(1H, dd, J=8.6 Hz, 1.5 Hz),7.60-7.30(6H, m), 6.85-6.70(2H, m), 5.03(2H, s), 4.02(1H, m), 3.95(3H,s), 2.35-2.10(2H, m), 2.05-1.70(5H, m), 1.40-1.20(3H, m)

EXAMPLE 338 Production of methyl2-[4-{5-amino-2-(4-chlorophenyl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate

Methyl2-[4-{2-(4-chlorophenyl)-5-nitrobenzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate(1.9 g) obtained in Example 337 was suspended in ethanol (40 ml), andtin(II) chloride dihydrate (3.5 g) was added, which was followed byrefluxing under heating for 30 min. The reaction mixture wasconcentrated under reduced pressure, 4N sodium hydroxide was added andthe mixture was extracted with chloroform. The organic layer was washedwith 2N sodium hydroxide and water, dried over anhydrous magnesiumsulfate and concentrated under reduced pressure. Diisopropyl ether wasadded to the residue, and the precipitated crystals were collected byfiltration to give the title compound (1.5 g, yield 82%).

¹H-NMR (300 MHz, CDCl₃): 8.49(1H, d, J=1.2 Hz), 7.98(1H, dd, J=9.0, 1.5Hz), 7.66(1H, d, J=8.7 Hz), 7.49(1H, t, J=8.4 Hz), 7.40-7.20(3H, m),7.13(1H, d, J=8.1 Hz), 6.92(1H, d, J=2.7 Hz), 6.85-6.65(4H, m), 4.92(2H,s), 4.03(1H, m), 3.95(3H, s), 3.82(2H, brs), 2.30-2.10(2H, m),2.05-1.80(4H, m), 1.80-1.70(1H, m), 1.40-1.10(3H, m)

EXAMPLE 339 Production of methyl2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate

Methyl2-[4-{5-amino-2-(4-chlorophenyl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate(500 mg) obtained in Example 338 and triethylamine (0.14 ml) weredissolved in chloroform (5 ml), and commercially available chlorobutyrylchloride (0.1 ml) was added under ice-cooling, which was followed bystirring at room temperature for 3 hr. Water was added to the reactionmixture and the mixture was extracted with ethyl acetate. The organiclayer was washed with water and saturated brine, dried over anhydrousmagnesium sulfate and concentrated under reduced pressure. The residuewas dissolved in dimethylformamide (6 ml) and potassium carbonate (244mg) was added, which was followed by stirring at 80° C. for 1 hr. Thereaction mixture was allowed to cool, water was added and theprecipitated crystals were collected by filtration to give the titlecompound (502 mg, yield 89%).

¹H-NMR (300 MHz, CDCl₃): 4.89(1H, d, J=1.5 Hz), 7.98(1H, dd, J=8.6 Hz,1.6 Hz), 7.72(1H, d, J=2.2 Hz), 7.75-7.65(2H, m), 7.49(1H, t, J=8.3 Hz),7.45-7.20(5H, m), 6.85-7.65(2H, m), 4.99(2H, s), 4.10-3.85(6H, m),2.66(2H, t, J=7.8 Hz), 2.30-2.15(4H, m), 2.00-1.85(4H, m), 1.80-1.70(1H,m), 1.45-1.20(3H, m)

EXAMPLE 340 Production of2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylicacid hydrochloride

Methyl2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate(200 mg) obtained in Example 339 was treated in the same manner as inExample 2 to give the title compound (182 mg, yield 87%).

Ms: 638(M+1)

¹H-NMR (300 MHz, CDCl₃): 8.28(1H, d, J=1.3 Hz), 8.10(1H, d, J=8.7 Hz),8.05-7.90(2H, m), 7.77(1H, dd, J=8.4 Hz, 2.2 Hz), 7.61(1H, t, J=8.5 Hz),7.55-7.35(5H, m), 7.00-7.20(2H, m), 5.09(2H, s), 4.06(1H, m), 3.90(2H,t, J=6.9 Hz), 2.60-2.45(2H, m), 2.30-2.00(4H, m), 1.95-1.75(4H, m),1.70-1.55(1H, m), 1.45-1.15(3H, m)

EXAMPLE 340-2 Step 1: Production of4′-chloro-4-nitro-biphenyl-2-carbaldehyde

To a solution of 2-chloro-5-nitrobenzaldehyde (100 g) in1,2-dimethoxyethane (1000 ml) were added 4-chlorophenylboronic acid (93g), bistriphenylphosphine palladium(II) dichloride (380 mg), sodiumhydrogencarbonate (68 g) and water (500 ml), and the mixture wasrefluxed for 1 hr. The reaction mixture was cooled to 50° C., ethylacetate (1000 ml) was added thereto and the mixture was stirred. Theaqueous layer was separated and the organic layer was washed with water(500 ml), 1N aqueous sodium hydroxide solution (500 ml), water (500 ml),28% aqueous ammonia (500 ml), water (500 ml), 2N hydrochloric acid (500ml) and saturated brine (500 ml), dried over anhydrous magnesium sulfateand concentrated under reduced pressure. The residue was suspended indiisopropyl ether (500 ml), filtrated and vacuum dried to give the titlecompound (120 g, yield 85%).

¹H-NMR (300 MHz, DMSO-d₆): 9.92(1H, s), 8.61 (1H, d, J=2.5 Hz), 8.53(1H,dd, J=2.6 Hz, 8.5 Hz), 7.82(1H, d, J=8.5 Hz), 7.64(2H, d, J=8.7 Hz),7.59(2H, d, J=8.7 Hz)

Step 2: Production of (4′-chloro-4-nitro-biphenyl-2-yl)methanol

A solution of 4′-chloro-4-nitro-biphenyl-2-carbaldehyde (120 g) obtainedin the previous step in tetrahydrofuran (900 ml) was added dropwise to asuspension of sodium borohydride (47 g) in 2-propanol (600 ml), over 70min under water-cooling. The reaction mixture was stirred at roomtemperature for 1 hr, and 2N hydrochloric acid (185 ml) was dropwiseadded thereto over 40 min under water-cooling. The mixture was stirredat room temperature for 30 min and concentrated under reduced pressure.The residue was suspended in 2-propanol (300 ml), and water (1000 ml)was added with stirring. After stirring the mixture for 30 min, thecrystals were collected by filtration and vacuum dried to give the titlecompound (116 g, yield 96%).

¹H-NMR (300 MHz, DMSO-d₆): 8.43(1H, d, J=2.5 Hz), 8.19(1H, dd, J=2.6 Hz,8.4 Hz), 7.57(2H, d, J=8.5 Hz), 7.52(1H, d, J=8.4 Hz), 7.47(2H, d, J=8.6Hz), 5.59(1H, brs), 4.48(2H, s)

Step 3: Production of (4-amino-4′-chloro-biphenyl-2-yl)methanol

To a suspension of (4′-chloro-4-nitro-biphenyl-2-yl)methanol (1.0 g)obtained in the previous step and sodium hydrosulfite (2.0 g) inN,N-dimethylformamide (4 ml) and methanol (1 ml) was added water (0.3ml, 50 μl each time in 6 portions) every 20 min at 100° C. Water (5 ml)was added threto at room temperature. Conc. hydrochloric acid (2.5 ml)was added threto at room temperature. The mixture was stirred at 55° C.for 2.5 hr, and a solution of sodium hydroxide (1.2 g) in water (3 ml)was added under ice-cooling. Water (5 ml) was added and the mixture wasstirred at room temperature for 1 hr. The precipitate was filtrated andwashed with water (3 ml). The crystals were vacuum dried to give thetitle compound (700 mg, yield 79%).

¹H-NMR (400 MHz, DMSO-d₆): 7.39(2H, d, J=8.5 Hz), 7.35(2H, d, J=8.5 Hz),6.90(1H, d, J=8.4 Hz), 6.82(1H, s), 6.56(1H, d, J=8.4 Hz), 5.20(2H,brs), 5.04(1H, t, J=5.4 Hz), 4.29(2H, d, J=5.4 Hz)

Step 4: Production of4-chloro-N-(4′-chloro-2-hydroxymethyl-biphenyl-4-yl)butyramide

To a solution of (4-amino-4′-chloro-biphenyl-2-yl)-methanol (1.0 g)obtained in the previous step in tetrahydrofuran (10 ml) were addedsodium acetate (390 mg) and acetic acid (0.27 ml) at room temperature.

4-Chlorobutyryl chloride (0.48 ml) was gradually added dropwise underice-cooling. After stirring the mixture at room temperature for 30 min,water (20 ml) and ethyl acetate (20 ml) were added to the reactionmixture and the organic layer was separated. The organic layer waswashed with saturated aqueous sodium hydrogencarbonate (20 ml) andsaturated brine (20 ml). The organic layer was dried over sodiumsulfate, filtrated and the solvent was evaporated to give the titlecompound (1.44 g, yield 99%).

¹H-NMR (300 MHz, CDCl₃): 7.68(1H, s), 7.55(1H, d, J=8.4 Hz), 7.39(2H, d,J=8.5 Hz), 7.28(2H, d, J=8.5 Hz), 7.22(1H, d, J=8.3 Hz), 4.58(2H, s),3.69(2H, t, J=6.1 Hz), 2.60(2H, t, J=7.0 Hz), 2.22(2H, m)

Step 5: Production of1-(4′-chloro-2-hydroxymethyl-biphenyl-4-yl)-2-pyrrolidinone

To a solution of4-chloro-N-(4′-chloro-2-hydroxymethyl-biphenyl-4-yl)butyramide (1.44 g)obtained in the previous step in N,N-dimethylformamide (15 ml) was addedpotassium carbonate (710 mg) at room temperature. After stirring themixture at 100° C. for 90 min, 1N hydrochloric acid (5 ml) and water (20ml) were added at room temperature and the precipitated crystals werecollected by filtration and washed with water (5 ml). The crystals werevacuum dried to give the title compound (970 mg, yield 76%).

¹H-NMR (300 MHz, CDCl₃): 7.76(1H, d, J=2.3 Hz), 7.62(1H, dd, J=2.4 Hz,8.3 Hz), 7.38(2H, d, J=8.5 Hz), 7.29(2H, d, J=8.5 Hz), 7.25(1H, d, J=8.3Hz), 4.61(2H, s), 3.91(2H, t, J=7.0 Hz), 2.62(2H, t, J=7.8 Hz), 2.18(2H,m)

Step 6: Production of1-(4′-chloro-2-chloromethyl-biphenyl-4-yl)-2-pyrrolidinone

To a mixed solution of1-(4′-chloro-2-hydroxymethyl-biphenyl-4-yl)-2-pyrrolidinone (900 mg)obtained in the previous step in N,N-dimethylformamide (2 ml) andtoluene (7 ml) was dropwise added thionyl chloride (0.26 ml) underice-cooling. After stirring the mixture at room temperature for 3 hr,the reaction mixture was diluted with ethyl acetate (20 ml) and washedwith water (20 ml), saturated aqueous sodium hydrogencarbonate (20 ml)and saturated brine (20 ml). The organic layer was dried over sodiumsulfate, filtrated and the solvent was evaporated under reduced pressureto give the title compound (954 mg, yield 99%).

¹H-NMR (300 MHz, CDCl₃): 7.77(1H, d, J=2.3 Hz), 7.69(1H, dd, J=2.4 Hz,8.5 Hz), 7.42(2H, d, J=8.6 Hz), 7.34(2H, d, J=8.6 Hz), 7.26(1H, d, J=8.4Hz), 4.50(2H, s), 3.92(2H, t, J=7.0 Hz), 2.65(2H, t, J=7.8 Hz), 2.20(2H,m)

Step 7: Production of methyl2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate

To a suspension of methyl1-cyclohexyl-2-(2-fluoro-4-hydroxyphenyl)benzimidazole-5-carboxylate(915 mg) obtained in Example 18 in N,N-dimethylformamide (6 ml) wasadded 1-(4′-chloro-2-chloromethyl-biphenyl-4-yl)-2-pyrrolidinone (954mg) obtained in the previous step and potassium carbonate (415 mg) atroom temperature. After stirring the mixture at 100° C. for 1 hr, 1Nhydrochloric acid (3 ml) and water (8 ml) were added at room temperatureand the precipitated crystals were collected by filtration and washedwith water (5 ml). The crystals were vacuum dried to give the titlecompound (1.6 g, yield 100%).

¹H-NMR (300 MHz, CDCl₃): 8.49(1H, d, J=1.5 Hz), 7.98(1H, dd, J=1.6 Hz,8.6 Hz), 7.90(1H, d, J=2.2 Hz), 7.72-7.65(2H, m), 7.49(1H, t, J=8.3 Hz),7.40(2H, d, J=8.5 Hz), 7.34(1H, d, J=8.7 Hz), 7.31(2H, d, J=8.6 Hz),6.80 (1H, d, J=8.6 Hz), 6.71(1H, d, J=11.6 Hz), 4.99(2H, s), 4.04(1H,m), 3.95(3H, s), 3.93(2H, t, J=7.1 Hz), 2.66(2H, t, J=7.8 Hz),2.30-2.15(4H, m), 2.00-1.85(4H, m), 1.80-1.70(1H, m), 1.45-1.20(3H, m)

Step 8: Production of2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylicacid

Methyl2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate(2.0 g) obtained in the previous step was suspended in methanol (4.0 ml)and tetrahydrofuran (8.0 ml), and 2N aqueous sodium hydroxide solution(2.3 ml) was added. The mixture was heated under reflux for 3 hr. Thereaction mixture was allowed to cool and tetrahydrofuran (1.0 ml) andwater (5.0 ml) were added. 2N Hydrochloric acid (2.3 ml) was graduallyadded at room temperature. After stirring the mixture at roomtemperature for 2 hr, the precipitated crystals were collected byfiltration and washed successively with methanol-water (1:1) mixedsolution (6.0 ml), water (6.0 ml) and methanol-water (1:1) mixedsolution (6.0 ml), and vacuum dried to give the title compound (1.84 g,yield 94%).

¹H-NMR (300 MHz, DMSO-d₆): 12.75(1H, brs), 8.26(1H, s), 7.99(1H, s),7.96(1H, d, J=9.0 Hz), 7.89(1H, d, J=9.0 Hz), 7.78(1H, dd, J=2.1 Hz, 8.4Hz), 7.54(1H, t, J=9.0 Hz), 7.49(2H, d, J=8.7 Hz), 7.45(2H, d, J=8.4Hz), 7.38(1H, d, J=8.4 Hz), 7.08(1H, dd, J=2.1 Hz, 12.0 Hz), 6.96(1H,dd, J=2.1 Hz, 8.7 Hz), 5.09(2H, s), 3.99(1H, m), 3.91(2H, t, J=6.6 Hz),2.54(2H, t, J=7.8 Hz), 2.30-2.00(4H, m), 1.95-1.50(5H, m), 1.45-1.20(3H,m)

Step 9: Production of2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidine-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylicacid hydrochloride

To 4N hydrochloric acid (50 ml) were successively added2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylicacid (10.0 g) obtained in the previous step and acetone-methyl ethylketone (3:2) mixed solution (20 ml). The mixture was stirred at 60° C.for 3 hr and at room temperature for 1 hr. The crystals were collectedby filtration, washed twice with acetone (10 ml) and vacuum dried togive the title compound (9.62 g, yield 91%).

melting point: 243-246° C.

Ms: 638(M+1)

¹H-NMR (300 MHz, DMSO-d₆): 8.33(1H, d, J=1.1 Hz), 8.21(1H, d, J=8.8 Hz),8.02(1H, d, J=8.8 Hz), 8.00(1H, d, J=2.2 Hz), 7.77(1H, dd, J=2.2 Hz, 8.4Hz), 7.68(1H, t, J=8.4 Hz), 7.50(2H, d, J=8.4 Hz), 7.45(2H, d, J=8.4Hz), 7.39(1H, d, J=8.4 Hz), 7.20(1H, dd, J=2.2 Hz, 12.1 Hz), 7.06(1H,dd, J=2.2 Hz, 8.8 Hz), 5.11(2H, s), 4.13(1H, m), 3.91(2H, t, J=7.0 Hz),2.54(2H, t, J=8.1 Hz), 2.40-2.05(4H, m), 2.00-1.75(4H, m), 1.70-1.55(1H,m), 1.50-1.20(3H, m)

In the same manner as in Examples 1-30, 241-248 and 336-340 andoptionally using other conventional methods, where necessary, thecompounds of Examples 31-240, 249-335, 341-471, 701-703 and 1001-1559were obtained. The chemical structures and properties are shown in Table1 to 177, 185 to 212, 219 to 221 and 225 to 269.

EXAMPLE 501 Production of methyl2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexyl-1H-indole-5-carboxylate

Step 1: Production of methyl 3-bromo-4-cyclohexylaminobenzoate

3-Bromo-4-fluorobenzoic acid (2.0 g) was dissolved in methanol (20 ml)and concentrated sulfuric acid (2 ml) was added. The mixture wasrefluxed for 3 hr. The reaction mixture was poured into ice-cold waterand extracted with ethyl acetate (50 ml). The organic layer was washedwith water (30 ml) and saturated brine (30 ml), and dried over sodiumsulfate. After filtration, the solvent was evaporated under reducedpressure. The residue was dissolved in dimethyl sulfoxide (20 ml) andcyclohexylamine (10.3 ml) was added. The mixture was stirred overnightat 120° C. The reaction mixture was poured into 10% aqueous citric acidsolution (100 ml) and extracted with ethyl acetate (100 ml). The organiclayer was washed with water (50 ml) and saturated brine (50 ml), anddried over sodium sulfate. After filtration, the solvent was evaporatedunder reduced pressure and the residue was purified by silica gel flashchromatography (developing solvent, n-hexane:ethyl acetate=10:1) to givethe title compound (2.6 g, yield 92%).

¹H-NMR (300 MHz, CDCl₃): 8.10(1H, d, J=1.9 Hz), 7.83(1H, dd, J=1.9 Hz,8.6 Hz), 6.59(1H, d, J=8.7 Hz), 4.73(1H, brd, J=7.3 Hz), 3.85(3H, s),3.38(1H, m), 2.10-2.00(2H, m), 1.90-1.20(8H, m)

Step 2: Production of4′-chloro-2-(4-iodophenoxymethyl)-4-methoxybiphenyl

4-Iodophenol (5.0 g) was dissolved in acetone (50 ml), and potassiumcarbonate (4.7 g) and 4′-chloro-2-chloromethyl-4-methoxybiphenyl (6.0 g)obtained in Example 241, Step 4 were added. The mixture was refluxed for10 hr. The reaction mixture was concentrated and 4N aqueous sodiumhydroxide solution (50 ml) was added. The precipitated crystals werecollected by filtration, washed with water, and dried under reducedpressure to give the title compound (10.0 g, yield 98%).

¹H-NMR (300 MHz, CDCl₃): 7.52(2H, d, J=8.9 Hz), 7.35(2H, d, J=8.5 Hz),7.27-7.20(3H, m), 7.12(1H, s), 6.95(1H, d, J=8.5 Hz), 6.62(2H, d, J=8.9Hz), 4.84(2H, s), 3.85(3H, s)

Step 3: Production of[4-(4′-chloro-4-methoxybiphenyl-2-ylmethoxy)phenylethynyl]trimethylsilane

4′-Chloro-2-(4-iodophenoxymethyl)-4-methoxybiphenyl (7.0 g) obtained inthe previous step was dissolved in acetonitrile (50 ml), andtrimethylsilylacetylene (2.3 g), tetrakis-(triphenylphosphine)palladiumcomplex (1.8 g), copper(I) iodide (0.6 g) and triethylamine (50 ml) wereadded. The mixture was stirred overnight at room temperature andconcentrated. Water (30 ml) was added and the mixture was extracted withethyl acetate (50 ml). The organic layer was washed with water (30 ml)and saturated brine (30 ml) and dried over sodium sulfate. Afterfiltration, the solvent was evaporated under reduced pressure and theresidue was purified by silica gel flash chromatography (developingsolvent, n-hexane:ethyl acetate=10:1) to give the title compound (5.1 g,yield 79%).

¹H-NMR (300 MHz, CDCl₃): 7.37(2H, d, J=8.9 Hz), 7.34(2H, d, J=8.2 Hz),7.28-7.21(3H, m), 7.13(1H, s), 6.94(1H, d, J=8.2 Hz), 6.75(2H, d, J=8.9Hz), 4.87(2H, s), 3.85(3H, s), 0.23(9H, s)

Step 4: Production of methyl3-[4-(4′-chloro-4-methoxybiphenyl-2-ylmethoxy)phenylethynyl]-4-cyclohexylaminobenzoate

[4-(4′-Chloro-4-methoxybiphenyl-2-ylmethoxy)phenylethynyl]-trimethylsilane(5.1 g) obtained in the previous step was dissolved in methanol (50 ml)and chloroform (50 ml), and potassium carbonate (2.5 g) was added. Themixture was stirred for 3 hr at room temperature and concentrated. Water(30 ml) was added and the mixture was extracted with ethyl acetate (50ml). The organic layer was washed with water (30 ml) and saturated brine(30 ml) and dried over sodium sulfate. After filtration, the solvent wasevaporated under reduced pressure to give white crystals (3.8 g). Thewhite crystals (2.3 g) were dissolved in acetonitrile (10 ml), andmethyl 3-bromo-4-cyclohexylamino-benzoate (1.0 g) obtained in Step 1,tetrakis(triphenyl-phosphine)palladium complex (0.4 g), copper(I) iodide(0.1 g) and triethylamine (10 ml) were added. The mixture was stirredovernight at 100° C. and concentrated under reduced pressure. Water (30ml) was added and the mixture was extracted with ethyl acetate (50 ml).The organic layer was washed with water (30 ml) and saturated brine (30ml), and dried over sodium sulfate. After filtration, the solvent wasevaporated under reduced pressure and the residue was purified by silicagel flash chromatography (developing solvent, n-hexane:ethylacetate=8:1) to give the title compound (0.9 g, yield 49%).

¹H-NMR (300 MHz, CDCl₃): 8.03(1H, s), 7.84(1H, d, J=8.7 Hz),7.42-7.22(7H, m), 7.15(1H, s), 6.95(1H, d, J=8.2 Hz), 6.85(2H, d, J=8.8Hz), 6.59(1H, d, J=8.8 Hz), 5.07(1H, brs), 4.91(2H, s), 3.86(3H, s),3.85(3H, s), 3.42(1H, m), 2.15-2.00(2H, m), 1.80-1.20(8H, m)

Step 5: Production of methyl2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexyl-1H-indole-5-carboxylate

Methyl3-[4-(4′-chloro-4-methoxybiphenyl-2-ylmethoxy)phenyl-ethynyl]-4-cyclohexylaminobenzoate(0.5 g) obtained in the previous step was dissolved inN,N-dimethylformamide (5 ml), and copper(I) iodide (0.17 g) was added.The mixture was refluxed for 3 hr at 180° C. The insoluble materialswere removed by filtration. Water (10 ml) was added and the mixture wasextracted with ethyl acetate (30 ml). The organic layer was washed withwater (10 ml) and saturated brine (10 ml), and dried over sodiumsulfate. After filtration, the solvent was evaporated under reducedpressure and the residue was purified by silica gel flash chromatography(developing solvent, n-hexane:ethyl acetate=8:1) to give the titlecompound (0.27 g, yield 55%).

¹H-NMR (300 MHz, CDCl₃): 8.34(1H, s), 7.85(1H, d, J=8.8 Hz), 7.62(1H, d,J=8.8 Hz), 7.40-7.18(8H, m), 7.00-6.94(3H, m), 6.48(1H, s), 4.95(2H, m),4.18(1H, m), 3.93(3H, s), 3.88(3H, s), 2.45-2.25(2H, m), 1.95-1.20(8H,m)

EXAMPLE 502 Production of2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexyl-1H-indole-5-carboxylicacid

Methyl2-{4-[2-(4-chlorophenyl)-5-methoxybenzyloxy]phenyl}-1-cyclohexyl-1H-indole-5-carboxylate(0.27 g) obtained in Example 501 was treated in the same manner as inExample 2 to give the title compound (0.19 g, yield 71%).

APCI-Ms: 566(MH+)

¹H-NMR (300 MHz, DMSO-d₆): 12.43(1H, brs), 8.20(1H, s), 7.79(1H, d,J=9.3 Hz), 7.72(1H, d, J=9.0 Hz), 7.50-7.20(8H, m), 7.07-7.03(3H, m),6.53(1H, s), 5.01(2H, s), 4.13(1H, m), 3.83(3H, m), 2.35-2.25(2H, m),1.85-1.10(8H, m)

In the same manner as in Examples 501 and 502, and optionally usingother conventional methods where necessary, the compound of Example 503was obtained. The chemical structure and properties are shown in Table207.

EXAMPLE 601 Production of ethyl2-(4-benzyloxyphenyl)-3-cyclohexylimidazo-[1,2-a]pyridine-7-carboxylate

Step 1: Production of 4-benzyloxy-N-methoxy-N-methylbenzamide

4-Benzyloxybenzoic acid (5.0 g) and N,O-dimethyl-hydroxylaminehydrochloride (2.5 g) were suspended in dimethylformamide (50 ml), and1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (5.0 g),1-hydroxybenzotriazole (3.5 g) and triethylamine (3.6 ml) were added.The mixture was stirred overnight at room temperature. Water was addedto the reaction mixture and the mixture was extracted with ethylacetate. The organic layer was washed successively with water, saturatedaqueous sodium hydrogencarbonate, water and saturated brine, and driedover anhydrous magnesium sulfate. The solvent was evaporated underreduced pressure to give the title compound (5.6 g, yield 94%).

¹H-NMR (300 MHz, CDCl₃): 7.22, 2H, d, J=8.8 Hz), 7.28-7.46(5H, m),6.97(2H, d, J=8.8 Hz), 5.10(2H, s), 3.56(3H, s), 3.35(3H, s)

Step 2: Production of 1-(4-benzyloxyphenyl)-2-cyclohexylethanone

Magnesium (470 mg) was suspended in tetrahydrofuran (2 ml) andcyclohexylmethyl bromide (3.4 g) was added dropwise at room temperature.After the addition, the reaction mixture was stirred for 30 min at 60°C. The reaction mixture was allowed to cool and diluted withtetrahydrofuran (5 ml). Separately,4-benzyloxy-N-methoxy-N-methylbenzamide (3.4 g) obtained in the previousstep was dissolved in tetrahydrofuran (10 ml) and the solution was addeddropwise to the reaction mixture at room temperature. The mixture wasstirred for 2 hr and saturated aqueous ammonium chloride solution wasadded to the reaction mixture. The mixture was extracted with diethylether. The organic layer was washed with saturated brine and dried overanhydrous magnesium sulfate, and the solvent was evaporated underreduced pressure. The residue was purified by silica gel flashchromatography (developing solvent, n-hexane:ethyl acetate=9:1) to givethe title compound (3.8 g, yield 66%).

¹H-NMR (300 MHz, CDCl₃): 7.93(2H, d, J=8.8 Hz), 7.28-7.46(5H, m),7.00(2H, d, J=8.8 Hz), 5.13(2H, s), 2.76(2H, d, J=6.8 Hz), 1.95(1H, m),0.78-1.82(10H, m)

Step 3: Production of 1-(4-benzyloxyphenyl)-2-bromo-2-cyclohexylethanone

1-(4-Benzyloxyphenyl)-2-cyclohexylethanone (1.0 g) obtained in theprevious step was dissolved in 1,4-dioxane (10 ml) and bromine (0.17 ml)was added. The mixture was stirred for 10 min at room temperature.Saturated aqueous sodium hydrogencarbonate was added to the reactionmixture and the mixture was extracted with diethyl ether. The organiclayer was washed with water and saturated brine and dried over anhydrousmagnesium sulfate, and the solvent was evaporated under reducedpressure. The residue was purified by silica gel flash chromatography(developing solvent, n-hexane:ethyl acetate=9:1) to give the titlecompound (696 mg, yield 55%).

¹H-NMR (300 MHz, CDCl₃): 7.98(2H, d, J=8.9 Hz), 7.28-7.48(5H, m),7.02(2H, d, J=8.9 Hz), 5.14(2H, s), 4.89(1H, d, J=9.3 Hz),0.86-3.30(11H, m)

Step 4: Production of ethyl2-(4-benzyloxyphenyl)-3-cyclohexylimidazo[1,2-a]pyridine-7-carboxylate

Ethyl 2-aminopyridine-4-carboxylate (214 mg) prepared according toJP-A-8-48651, 1-(4-benzyloxyphenyl)-2-bromo-2-cyclohexylethanone (500mg) obtained in the previous step and potassium carbonate (356 mg) werestirred for 5 hr with heating at 140° C. The reaction mixture wasallowed to cool and chloroform was added. The insoluble materials werefiltered off and the filtrate was concentrated under reduced pressure.The residue was purified by silica gel flash chromatography (developingsolvent, n-hexane:ethyl acetate=1:1) to give the title compound (95 mg,yield 16%).

APCI-MS: 455(MH+)

¹H-NMR (300 MHz, CDCl₃): 8.33(1H, s), 8.21(1H, d, J=7.5 Hz), 7.55(2H, d,J=8.7 Hz), 7.25-7.50(6H, m), 5.13(2H, s), 4.41(2H, q, J=7.1 Hz),3.25(1H, m), 1.41(3H, t, J=7.1 Hz), 1.15-2.00(10H, m)

EXAMPLE 602 Production of2-(4-benzyloxyphenyl)-3-cyclohexylimidazo[1,2-a]pyridine-7-carboxylicacid

Ethyl2-(4-benzyloxyphenyl)-3-cyclohexylimidazo[1,2-a]pyridine-7-carboxylate(95 mg) obtained in the previous step was treated in the same manner asin Example 2 to give the title compound (33 mg, 37%).

APCI-MS: 427(MH+)

¹H-NMR (300 MHz, DMSO-d₆): 8.67(1H, d, J=7.3 Hz), 8.08(1H, s),7.25-7.58(8H, m), 7.13(2H, d, J=8.7 Hz), 5.17(2H, s), 3.23(1H, m),1.25-2.10(10H, m)

The compounds shown in Tables 213 to 218 can be further obtained in thesame manner as in Examples 1 to 703 or by other conventional methodemployed as necessary.

The evaluation of the HCV polymerase inhibitory activity of the compoundof the present invention is explained in the following. This polymeraseis an enzyme coded for by the non-structural protein region called NS5Bon the RNA gene of HCV (EMBO J., 15:12-22, 1996).

EXPERIMENTAL EXAMPLE [I]

i) Preparation of Enzyme (HCV Polymerase)

Using, as a template, a cDNA clone corresponding to the full length RNAgene of HCV BK strain obtained from the blood of a patient withhepatitis C, a region encoding NS5B (591 amino acids; J Virol 1991March, 65(3), 1105-13) was amplified by PCR. The objective gene wasprepared by adding a 6 His tag {base pair encoding 6 continuoushistidine (His)} to the 5′ end thereof and transformed to Escherichiacoli. The Escherichia coli capable of producing the objective proteinwas cultured. The obtained cells were suspended in a buffer solutioncontaining a surfactant and crushed in a microfluidizer. The supernatantwas obtained by centrifugation and applied to various columnchromatographys {poly[U]-Sepharose, Sephacryl S-200, mono-S(Pharmacia)}, inclusive of metal chelate chromatography, to give astandard enzyme product.

ii) Synthesis of Substrate RNA

Using a synthetic primer designed based on the sequence of HCV genomic3′ untranslated region, a DNA fragment (148 bp) containing polyU and 3′Xsequence was entirely synthesized and cloned into plasmid pBluescript SKII(+) (Stratagene). The cDNA encoding full length NS5B, which wasprepared in i) above, was digested with restriction enzyme KpnI to givea cDNA fragment containing the nucleotide sequence of from therestriction enzyme cleavage site to the termination codon. This cDNAfragment was inserted into the upstream of 3′ untranslated region of theDNA in pBluescript SK II(+) and ligated. The about 450 bp inserted DNAsequence was used as a template in the preparation of substrate RNA.This plasmid was cleaved immediately after the 3′X sequence, linearizedand purified by phenol-chloroform treatment and ethanol precipitation togive DNA.

RNA was synthesized (37° C., 3 hr) by run-off method using this purifiedDNA as a template, a promoter of pBluescript SK II(+), MEGAscript RNAsynthesis kit (Ambion) and T7 RNA polymerase. DNaseI was added and themixture was incubated for 1 hr. The template DNA was removed bydecomposition to give a crude RNA product. This product was treated withphenol-chloroform and purified by ethanol precipitation to give theobjective substrate RNA.

This RNA was applied to formaldehyde denaturation agarose gelelectrophoresis to confirm the quality thereof and preserved at −80° C.

iii) Assay of Enzyme (HCV Polymerase) Inhibitory Activity

A test substance (compound of the present invention) and a reactionmixture (30 μl) having the following composition were reacted at 25° C.for 90 min.

10% Trichloroacetic acid at 4° C. and 1% sodium pyrophosphate solution(150 μl) were added to this reaction mixture to stop the reaction. Thereaction mixture was left standing in ice for 15 min to insolubilizeRNA. This RNA was trapped on a glass filter (Whatman GF/C and the like)upon filtration by suction. This filter was washed with a solutioncontaining 1% trichloroacetic acid and 0.1% sodium pyrophosphate, washedwith 90% ethanol and dried. A liquid scintillation cocktail (Packard)was added and the radioactivity of RNA synthesized by the enzymereaction was measured on a liquid scintillation counter.

The HCV polymerase inhibitory activity (IC₅₀) of the compound of thepresent invention was calculated from the values of radioactivity of theenzyme reaction with and without the test substance.

The results are shown in Tables 178-184 and 222-224.

Reaction mixture: HCV polymerase (5 μg/ml) obtained in i), substrate RNA(10 μg/ml) obtained in ii), ATP (50 μM), GTP (50 μM), CTP (50 μM), UTP(2 μM), [5,6-³H]UTP (46 Ci/mmol (Amersham), 1.5 μCi) 20 mM Tris-HCl (pH7.5), EDTA (1 mM), MgCl₂ (5 mM), NaCl (50 mM), DTT (1 mM), BSA (0.01%)

Formulation Example is given in the following. This example is merelyfor the purpose of exemplification and does not limit the invention.

FORMULATION EXAMPLE

(a) compound of Example 1 10 g (b) lactose 50 g (c) corn starch 15 g (d)sodium carboxymethylcellulose 44 g (e) magnesium stearate 1 g

The entire amounts of (a), (b) and (c) and 30 g of (d) are kneaded withwater, dried in vacuo and granulated. The obtained granules are mixedwith 14 g of (d) and 1 g of (e) and processed into tablets with atableting machine to give 1000 tablets each containing 10 mg of (a).LENGTHY TABLE REFERENCED HERE US20070032497A1-20070208-T00001 Pleaserefer to the end of the specification for access instructions. LENGTHYTABLE REFERENCED HERE US20070032497A1-20070208-T00002 Please refer tothe end of the specification for access instructions. LENGTHY TABLEREFERENCED HERE US20070032497A1-20070208-T00003 Please refer to the endof the specification for access instructions. LENGTHY TABLE REFERENCEDHERE US20070032497A1-20070208-T00004 Please refer to the end of thespecification for access instructions. LENGTHY TABLE REFERENCED HEREUS20070032497A1-20070208-T00005 Please refer to the end of thespecification for access instructions. 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INDUSTRIAL APPLICABILITY

As is evident from the above-mentioned results, the compound of thepresent invention shows a high inhibitory activity against HCVpolymerase.

Therefore, the compound of the present invention can provide apharmaceutical agent effective for the prophylaxis or treatment ofhepatitis C, based on the anti-HCV effect afforded by the HCV polymeraseinhibitory activity. When used concurrently with a different anti-HCVagent, such as interferon, and/or an anti-inflammatory agent and thelike, it can provide a pharmaceutical agent more effective for theprophylaxis or treatment of hepatitis C. Its high inhibitory activityspecific to HCV polymerase suggests the possibility of the compoundbeing a pharmaceutical agent with slight side effects, which can be usedsafely for humans.

This application is based on patent application Nos. 369008/1999,391904/2000, 193786/2001 and 351537/2001 filed in Japan, internationalapplication No. PCT/JP00/09181 and U.S. patent application Ser. No.09/939,374, the contents of which are hereby incorporated by reference.LENGTHY TABLE The patent application contains a lengthy table section. Acopy of the table is available in electronic form from the USPTO website(http://seqdata.uspto.gov/?pageRequest=docDetail&DocID=US20070032497A1)An electronic copy of the table will also be available from the USPTOupon request and payment of the fee set forth in 37 CFR 1.19(b)(3).

1. A therapeutic agent for hepatitis C, which comprises a fused ringcompound of the following formula [I] or a pharmaceutically acceptablesalt thereof as an active ingredient:

wherein a broken line is a single bond or a double bond, G¹ is C(—R¹) ora nitrogen atom, G² is C(—R²) or a nitrogen atom, G³ is C(—R³) or anitrogen atom, G⁴ is C(—R¹) or a nitrogen atom, G⁵, G⁶, G⁸ and G⁹ areeach independently a carbon atom or a nitrogen atom, G⁷ is C(—R⁷), anoxygen atom, a sulfur atom, or a nitrogen atom optionally substituted byR⁸, wherein R¹, R², R³ and R⁴ are each independently, (1) hydrogen atom,(2) C₁₋₆ alkanoyl, (3) carboxyl, (4) cyano, (5) nitro, (6) C₁₋₆ alkyloptionally substituted by 1 to 3 substituent(s) selected from thefollowing group A, group A; halogen atom, hydroxyl group, carboxyl,amino, C₁₋₆ alkoxy, C₁₋₆ alkoxy C₁₋₆ alkoxy, C₁₋₆ alkoxycarbonyl andC₁₋₆ alkylamino, (7) —COOR^(a1) wherein R^(a1) is optionally substitutedC₁₋₆ alkyl (as defined above), C₆₋₁₄ aryl C₁₋₆ alkyl optionallysubstituted by 1 to 5 substituent(s) selected from the following group Bor glucuronic acid residue, group B; halogen atom, cyano, nitro, C₁₋₆alkyl, halogenated C₁₋₆ alkyl, C₁₋₆ alkanoyl, —(CH₂)_(r)—COOR^(b1),—(CH₂)_(r)—CONR^(b1)R^(b2), —(CH₂)_(r)—NR^(b1)R^(b2),—(CH₂)_(r)—NR^(b1)—COR^(b2), —(CH₂)_(r)—NHSO₂R^(b1), —(CH₂)_(r)—OR^(b1),—(CH₂)_(r)—SR^(b1), —(CH₂)_(r)—SO₂R^(b1) and —(CH₂)_(r)—SO₂NR^(b1)R^(b2)wherein R^(b1) and R^(b2) are each independently hydrogen atom or C₁₋₆alkyl and r is 0 or an integer of 1 to 6, (8) —CONR^(a2)R^(a3) whereinR^(a2) and R^(a3) are each independently hydrogen atom, C₁₋₆ alkoxy oroptionally substituted C₁₋₆ alkyl (as defined above), (9)—C(═NR^(a4))NH₂ wherein R^(a4) is hydrogen atom or hydroxyl group, (10)—NHR^(a5) wherein R^(a5) is hydrogen atom, C₁₋₆ alkanoyl or C₁₋₆alkylsulfonyl, (11) —OR^(a6) wherein R^(a6) is hydrogen atom oroptionally substituted C₁₋₆ alkyl(as defined above), (12) —SO₂R^(a7)wherein R^(a7) is hydroxyl group, amino, C₁₋₆ alkyl or C₁₋₆ alkylamino,(13) —P(═O)(OR^(a31))₂ wherein R^(a31) is hydrogen atom, optionallysubstituted C₁₋₆ alkyl (as defined above) or C₆₋₁₄ aryl C₁₋₆ alkyloptionally substituted by 1 to 5 substituent(s) selected from the abovegroup B or (14) heterocyclic group having 1 to 4 heteroatom(s) selectedfrom an oxygen atom, a nitrogen atom and a sulfur atom, and R⁷ and R⁸are each hydrogen atom or optionally substituted C₁₋₆ alkyl (as definedabove), ring Cy is (1) C₃₋₈ cycloalkyl optionally substituted by 1 to 5substituent(s) selected from the following group C, group C; hydroxylgroup, halogen atom, C₁₋₆ alkyl and C₁₋₆ alkoxy, (2) C₃₋₈ cycloalkenyloptionally substituted by 1 to 5 substituent(s) selected from the abovegroup C, or

wherein u and v are each independently an integer of 1 to 3, ring A is(1) C₆₋₁₄ aryl, (2) C₃₋₈ cycloalkyl, (3) C₃₋₈ cycloalkenyl or (4)heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygenatom, a nitrogen atom and a sulfur atom, R⁵ and R⁶ are eachindependently (1) hydrogen atom, (2) halogen atom, (3) optionallysubstituted C₁₋₆ alkyl (as defined above) or (4) —OR^(a8) wherein R^(a8)is hydrogen atom, C₁₋₆ alkyl or C₆₋₁₄ aryl C₁₋₆ alkyl, and X is (1)hydrogen atom, (2) halogen atom, (3) cyano, (4) nitro, (5) amino, C₁₋₆alkanoylamino, (6) C₁₋₆ alkylsulfonyl, (7) optionally substituted C₁₋₆alkyl (as defined above), (8) C₂₋₆ alkenyl optionally substituted by 1to 3 substituent(s) selected from the above group A, (9) —COOR^(a9)wherein R^(a9) is hydrogen atom or C₁₋₆ alkyl, (10)—CONH—(CH₂)_(l)—R^(a10) wherein R^(a10) is optionally substituted C₁₋₆alkyl (as defined above), C₁₋₆ alkoxycarbonyl or C₁₋₆ alkanoylamino andl is 0 or an integer of 1 to 6, (11) —OR^(a11) wherein R^(a11) ishydrogen atom or optionally substituted C₁₋₆ alkyl (as defined above) or

wherein ring B is (1′) C₆₋₁₄ aryl, (2′) C₃₋₈ cycloalkyl or (3′)heterocyclic group (as defined above), each Z is independently (1′) agroup selected from the following group D, (2′) C₆₋₁₄ aryl optionallysubstituted by 1 to 5 substituent(s) selected from the following groupD, (3′) C₃₋₈ cycloalkyl optionally substituted by 1 to 5 substituent(s)selected from the following group D, (4′) C₆₋₁₄ aryl C₁₋₆ alkyloptionally substituted by 1 to 5 substituent(s) selected from thefollowing group D, (5′) heterocyclic group optionally substituted by 1to 5 substituent(s) selected from the following group D, wherein theheterocyclic group has 1 to 4 hetero-atom(s) selected from an oxygenatom, a nitrogen atom and a sulfur atom, or (6′) heterocycle C₁₋₆ alkyloptionally substituted by 1 to 5 substituent(s) selected from thefollowing group D, wherein the heterocycle C₁₋₆ alkyl is C₁₋₆ alkylsubstituted by heterocyclic group optionally substituted by 1 to 5substituent(s) selected from the group D, as defined above, group D: (a)hydrogen atom, (b) halogen atom, (c) cyano, (d) nitro, (e) optionallysubstituted C₁₋₆ alkyl (as defined above), (f) —(CH₂)_(t)—COR^(a18),(hereinafter each t means independently 0 or an integer of 1 to 6),wherein R^(a18) is (1″) optionally substituted C₁₋₆ alkyl (as definedabove), (2″) C₆₋₁₄ aryl optionally substituted by 1 to 5 substituent(s)selected from the above group B or (3″) heterocyclic group optionallysubstituted by 1 to 5 substituent(s) selected from the above group B wherein the heterocyclic group has 1 to 4 heteroatom(s) selected froman oxygen atom, a nitrogen atom and a sulfur atom, (g)—(CH₂)_(t)—COOR^(a19) wherein R^(a19) is hydrogen atom, optionallysubstituted C₁₋₆ alkyl (as defined above) or C₆₋₁₄ aryl C₁₋₆ alkyloptionally substituted by 1 to 5 substituent(s) selected from the abovegroup B (h) —(CH₂)_(t)—CONR^(a27)R^(a28) wherein R^(a27) and R^(a28) areeach independently,  (1″) hydrogen atom,  (2″) optionally substitutedC₁₋₆ alkyl (as defined above),  (3″) C₆₋₁₄ aryl optionally substitutedby 1 to 5 substituent(s) selected from the above group B,  (4″) C₆₋₁₄aryl C₁₋₆ alkyl optionally substituted by 1 to 5 substituent(s) selectedfrom the above group B,  (5″) heterocyclic group optionally substitutedby 1 to 5 substituent(s) selected from the above group B,  (6″)heterocycle C₁₋₆ alkyl optionally substituted by 1 to 5 substituent(s)selected from the above group B, wherein the heterocycle C₁₋₆ alkyl isC₁₋₆ alkyl substituted by heterocyclic group optionally substituted by 1to 5 substituent(s) selected from the above group B, as defined above, (7″) C₃₋₈ cycloalkyl optionally substituted by 1 to 5 substituent(s)selected from the above group B,  (8″) C₃₋₈ cycloalkyl C₁₋₆ alkyloptionally substituted by 1 to 5 substituent(s) selected from the abovegroup B,  (9″) hydroxyl group or  (10″) C₁₋₆ alkoxy, (i)—(CH₂)_(t)—C(═NR^(a33))NH₂ wherein R^(a33) is hydrogen atom, C₁₋₆ alkyl,hydroxyl group or C₁₋₆ alkoxy, (j) —(CH₂)_(t)—OR^(a20) wherein R^(a20)is (1″) hydrogen atom, (2″) optionally substituted C₁₋₆ alkyl (asdefined above), (3″) optionally substituted C₂₋₆ alkenyl (as definedabove), (4″) C₂₋₆ alkynyl optionally substituted by 1 to 3substituent(s) selected from the above group A, (5″) C₆₋₁₄ aryloptionally substituted by 1 to 5 substituent(s) selected from the abovegroup B, (6″) C₆₋₁₄ aryl C₁₋₆ alkyl optionally substituted by 1 to 5substituent(s) selected from the above group B, (7″) heterocyclic groupoptionally substituted by 1 to 5 substituent(s) selected from the abovegroup B, (8″) heterocycle C₁₋₆ alkyl optionally substituted by 1 to 5substituent(s) selected from the above group B, (9″) C₃₋₈ cycloalkyloptionally substituted by 1 to 5 substituent(s) selected from the abovegroup B, or (10″) C₃₋₈ cycloalkyl C₁₋₆ alkyl optionally substituted by 1to 5 substituent(s) selected from the above group B, (k)—(CH₂)_(t)—O—(CH₂)_(p)—COR^(a21)′ wherein R^(a21) is amino, C₁₋₆alkylamino or heterocyclic group optionally substituted by 1 to 5substituent(s) selected from the above group B, and p is 0 or an integerof 1 to 6, (l) —(CH₂)_(p)—NR^(a22)R^(a23) wherein R^(a22) and R^(a23)are each independently (1″) hydrogen atom, (2″) optionally substitutedC₁₋₆ alkyl (as defined above), (3″) C₆₋₁₄ aryl optionally substituted by1 to 5 substituent(s) selected from the above group B, (4″) C₆₋₁₄ arylC₁₋₆ alkyl optionally substituted by 1 to 5 substituent(s) selected fromthe above group B, (5″) heterocycle C₁₋₆ alkyl optionally substituted by1 to 5 substituent(s) selected from the above group B or (6″)heterocyclic group optionally substituted by 1 to 5 substituent(s)selected from the above group B, (m) —(CH₂)_(t)—NR^(a29)CO—R^(a24)wherein R^(a29) is hydrogen atom, C₁₋₆ alkyl or C₁₋₆ alkanoyl, andR^(a24) is (1″) amino, (2″) C₁₋₆ alkylamino, (3″) optionally substitutedC₁₋₆ alkyl (as defined above), (4″) C₆₋₁₄ aryl optionally substituted by1 to 5 substituent(s) selected from the above group B, (5″) heterocyclicgroup optionally substituted by 1 to 5 substituent(s) selected from theabove group B or (6″) heterocycle C₁₋₆ alkyl optionally substituted by 1to 5 substituent(s) selected from the above group B, (n)—(CH₂)_(t)—NR^(a29)SO₂—R^(a25) wherein R^(a29) is as defined above, andR^(a25) is hydrogen atom, optionally substituted C₁₋₆ alkyl (as definedabove), C₆₋₁₄ aryl optionally substituted by 1 to 5 substituent(s)selected from the above group B or heterocyclic group optionallysubstituted by 1 to 5 substituent(s) selected from the above group B,(o) —(CH₂)_(t)—S(O)_(q)—R^(a25) wherein R^(a25) is as defined above, andq is 0, 1 or 2, (p) —(CH₂)_(t)—SO₂—NHR^(a26) wherein R^(a26) is hydrogenatom, optionally substituted C₁₋₆ alkyl (as defined above), C₆₋₁₄ aryloptionally substituted by 1 to 5 substituent(s) selected from the abovegroup B or heterocyclic group optionally substituted by 1 to 5substituent(s) selected from the above group B, and (q) heterocyclicgroup having 1 to 4 heteroatom(s) selected from an oxygen atom, anitrogen atom and a sulfur atom, and w is an integer of 1 to 3, and Y is(1′) a single bond, (2′) C₁₋₆ alkylene, (3′) C₂₋₆ alkenylene, (4′)—(CH₂)_(m)—O—(CH₂)_(n)—, (hereinafter m and n are each independently 0or an integer of 1 to 6), (5′) —CO—, (6′) —CO₂—(CH₂)_(n)—, (7′)—CONH—(CH₂)_(n)—NH—, (8′) —NHCO₂—, (9′) —NHCONH—, (10′)—O—(CH₂)_(n)—CO—, (11′) —O—(CH₂)_(n)—O—, (12′) —SO₂—, (13′)—(CH₂)_(m)—NR^(a12) (CH₂)_(n), wherein R^(a12) is (1″) hydrogen atom,(2″) optionally substituted C₁₋₆ alkyl (as defined above), (3″) C₆₋₁₄aryl C₁₋₆ alkyl optionally substituted by 1 to 5 substituent(s) selectedfrom the above group B, (4″) C₆₋₁₄ aryl optionally substituted by 1 tosubstituent(s) selected from the above group B, (5″) —COR^(b5)  whereinR^(b5) is hydrogen atom, optionally substituted C₁₋₆ alkyl (as definedabove), C₆₋₁₄ aryl optionally substituted by 1 to 5 substituent(s)selected from the above group B or C₆₋₁₄ aryl C₁₋₆ alkyl optionallysubstituted by 1 to 5 substituent(s) selected from the above group B,(6″) —COOR^(b5) (R^(b5) is as defined above) or (7″) —SO₂R^(b5) (R^(b5)is as defined above), (14′) —NR^(a12)CO— (R^(a12) is as defined above),(15′) —CONR^(a13)—(CH₂)_(n)— wherein R^(a13) is hydrogen atom,optionally substituted C₁₋₆ alkyl (as defined above) or C₆₋₁₄ aryl C₁₋₆alkyl optionally substituted by 1 to 5 substituent(s) selected from theabove group B, (16′) —CONH—CHR^(a14)— wherein R^(a14) is C₆₋₁₄ aryloptionally substituted by 1 to 5 substituent(s) selected from the abovegroup B, (17′) —O—(CH₂)_(m)—CR^(a15)R^(a16)—(CH₂)_(n)— wherein R^(a15)and R^(a16) are each independently (1″) hydrogen atom, (2″) carboxyl,(3″) C₁₋₆ alkyl, (4″) —OR^(b6) wherein R^(b6) is C₁₋₆ alkyl or C₆₋₁₄aryl C₁₋₆ alkyl, or (5″) —NHR^(b7) wherein R^(b7) is hydrogen atom, C₁₋₆alkyl, C₁₋₆ alkanoyl or C₆₋₁₄ aryl C₁₋₆ alkyloxycarbonyl, or R^(a15) isoptionally

 wherein n′, ring B′, Z′ and w′ are the same as the above-mentioned n,ring B, Z and w, respectively, and may be the same as or different fromthe respective counterparts, (18′) —(CH₂)_(n)—NR^(a12)—CHR^(a15)—(R^(a12) and R^(a15) are each as defined above), (19′) —NR^(a17)SO₂—wherein R^(a17) is hydrogen atom or C₁₋₆ alkyl, (20′)—S(O)_(e)—(CH₂)_(m)—CR^(a15)R^(a16)—(CH₂)_(n)— (e is 0, 1 or 2, R^(a15)and R^(a16) are each as defined above), or (21′)—(CH₂)_(m)—CR^(a15)R^(a16)—(CH₂)_(n)— (R^(a15) and R^(a16) are each asdefined above). 2.-28. (canceled)
 29. A fused ring compound of thefollowing formula [II]

wherein the moiety

is a fused ring selected from

wherein R¹, R², R³ and R⁴ are each independently, (1) hydrogen atom, (2)C₁₋₆ alkanoyl, (3) carboxyl, (4) cyano, (5) nitro, (6) C₁₋₆ alkyloptionally substituted by 1 to 3 substituent(s) selected from thefollowing group A, group A; halogen atom, hydroxyl group, carboxyl,amino, C₁₋₆ alkoxy, C₁₋₆ alkoxy C₁₋₆ alkoxy, C₁₋₆ alkoxycarbonyl andC₁₋₆ alkylamino, (7) —COOR^(a1) wherein R^(a1) is optionally substitutedC₁₋₆ alkyl (as defined above), C₆₋₁₄ aryl C₁₋₆ alkyl optionallysubstituted by 1 to 5 substituent(s) selected from the following group Bor glucuronic acid residue, group B; halogen atom, cyano, nitro, C₁₋₆alkyl, halogenated C₁₋₆ alkyl, C₁₋₆ alkanoyl, —(CH₂)_(r)—COOR^(b1),—(CH₂)_(r)—CONR^(b1)R^(b2), —(CH₂)_(r)—NR^(b1)R^(b2),—(CH₂)_(r)—NR^(b1)—COR^(b2), —(CH₂)_(r)—NHSO₂R^(b1), —(CH₂)_(r)—OR^(b1),—(CH₂)_(r)—SR^(b1), —(CH₂)_(r)—SO₂R^(b1) and —(CH₂)_(r)—SO₂NR^(b1)R^(b2)wherein R^(b1) and R^(b2) are each independently hydrogen atom or C₁₋₆alkyl and r is 0 or an integer of 1 to 6, (8) —CONR^(a2)R^(a3) whereinR^(a2) and R^(a3) are each independently hydrogen atom, C₁₋₆ alkoxy oroptionally substituted C₁₋₆ alkyl (as defined above), (9)—C(═NR^(a4))NH₂ wherein R^(a4) is hydrogen atom or hydroxyl group, (10)—NHR^(a5) wherein R^(a5) is hydrogen atom, C₁₋₆ alkanoyl or C₁₋₆alkylsulfonyl, (11) —OR^(a6) wherein R^(a6) is hydrogen atom oroptionally substituted C₁₋₆ alkyl (as defined above), (12) —SO₂R^(a7)wherein R^(a7) is hydroxyl group, amino, C₁₋₆ alkyl or C₁₋₆ alkylamino,(13) —P(═O)(OR^(a31))₂ wherein R^(a31) is hydrogen atom, optionallysubstituted C₁₋₆ alkyl (as defined above) or C₆₋₁₄ aryl C₁₋₆ alkyloptionally substituted by 1 to 5 substituent(s) selected from the abovegroup B, or (14) heterocyclic group having 1 to 4 heteroatom(s) selectedfrom an oxygen atom, a nitrogen atom and a sulfur atom, and R⁷ ishydrogen atom or optionally substitute C₁₋₆ alkyl (as defined above),ring Cy′ is (1) C₃₋₈ cycloalkyl optionally substituted by 1 to 5substituent(s) selected from the following group C, group C; hydroxylgroup, halogen atom, C₁₋₆ alkyl and C₁₋₆ alkoxy, or

wherein u and v are each independently an integer of 1 to 3, ring A′ isa group selected from a group consisting of phenyl, pyridyl, pyrazinyl,pyrimidinyl, pyridazinyl, cyclohexyl, cyclohexenyl, furyl and thienyl,R^(5′) and R^(6′) are each independently (1) hydrogen atom, (2) halogenatom, (3) optionally substituted C₁₋₆ alkyl (as defined above) or (4)hydroxyl group ring B is (1) C₆₋₁₄ aryl, (2) C₃₋₈ cycloalkyl or (3)heterocyclic group having 1 to 4 heteroatom(s) selected from an oxygenatom, a nitrogen atom and a sulfur atom, each Z is independently (1) agroup selected from the following group D, (2) C₆₋₁₄ aryl optionallysubstituted by 1 to 5 substituent(s) selected from the following groupD, (3) C₃₋₈ cycloalkyl optionally substituted by 1 to 5 substituent(s)selected from the following group D, (4) C₆₋₁₄ aryl C₁₋₆ alkyloptionally substituted by 1 to 5 substituent(s) selected from thefollowing group D, (5) heterocyclic group optionally substituted by 1 to5 substituent(s) selected from the following group D wherein theheterocyclic group has 1 to 4 heteroatom(s) selected from an oxygenatom, a nitrogen atom and a sulfur atom, or (6) heterocycle C₁₋₆ alkyloptionally substituted by 1 to 5 substituent(s) selected from thefollowing group D wherein the heterocycle C₁₋₆ alkyl is C₁₋₆ alkylsubstituted by heterocyclic group optionally substituted by 1 to 5substituent(s) selected from the group D, as defined above, group D: (a)hydrogen atom, (b) halogen atom, (c) cyano, (d) nitro, (e) optionallysubstituted C₁₋₆ alkyl (as defined above), (f) —(CH₂)_(t)—COR^(a18),(hereinafter each t means independently 0 or an integer of 1 to 6), wherein R^(a18) is  (1′) optionally substituted C₁₋₆ alkyl (as definedabove),  (2′) C₆₋₁₄ aryl optionally substituted by 1 to 5 substituent(s)selected from the above group B or  (3′) heterocyclic group optionallysubstituted by 1 to 5 substituent(s) selected from the above group B wherein the heterocyclic group has 1 to 4 heteroatom(s) selected froman oxygen atom, a nitrogen atom and a sulfur atom, (g)—(CH₂)_(t)—COOR^(a19) wherein R^(a19) is hydrogen atom, optionallysubstituted C₁₋₆ alkyl (as defined above) or C₆₋₁₄ aryl C₁₋₆ alkyloptionally substituted by 1 to 5 substituent(s) selected from the abovegroup B, (h) —(CH₂)_(t)—CONR^(a27)R^(a28) wherein R^(a27) and R^(a28)are each independently,  (1′) hydrogen atom,  (2′) optionallysubstituted C₁₋₆ alkyl (as defined above),  (3′) C₆₋₁₄ aryl optionallysubstituted by 1 to 5 substituent(s) selected from the above group B, (4′) C₆₋₁₄ aryl C₁₋₆ alkyl optionally substituted by 1 to 5substituent(s) selected from the above group B,  (5′) heterocyclic groupoptionally substituted by 1 to 5 substituent(s) selected from the abovegroup B,  (6′) heterocycle C₁₋₆ alkyl optionally substituted by 1 to 5substituent(s) selected from the above group B, wherein the heterocycleC₁₋₆ alkyl is C₁₋₆ alkyl substituted by heterocyclic group optionallysubstituted by 1 to 5 substituent(s) selected from the above group B, asdefined above,  (7′) C₃₋₈ cycloalkyl optionally substituted by 1 to 5substituent(s) selected from the above group B,  (8′) C₃₋₈ cycloalkylC₁₋₆ alkyl optionally substituted by 1 to 5 substituent(s) selected fromthe above group B,  (9′) hydroxyl group or  (10′) C₁₋₆ alkoxy, (i)—(CH₂)_(t)—C(═NR^(a33))NH₂ wherein R^(a33) is hydrogen atom, C₁₋₆ alkyl,hydroxyl group or C₁₋₆ alkoxy, (j) —(CH₂)_(t)—OR^(a20) wherein R^(a20)is (1′) hydrogen atom, (2′) optionally substituted C₁₋₆ alkyl (asdefined above), (3′) optionally substituted C₂₋₆ alkenyl (as definedabove), (4′) C₂₋₆ alkynyl optionally substituted by 1 to 3substituent(s) selected from the above group A, (5′) C₆₋₁₄ aryloptionally substituted by 1 to 5 substituent(s) selected from the abovegroup B, (6′) C₆₋₁₄ aryl C₁₋₆ alkyl optionally substituted by 1 to 5substituent(s) selected from the above group B, (7′) heterocyclic groupoptionally substituted by 1 to 5 substituent(s) selected from the abovegroup B, (8′) heterocycle C₁₋₆ alkyl optionally substituted by 1 to 5substituent(s) selected from the above group B, (9′) C₃₋₈ cycloalkyloptionally substituted by 1 to 5 substituent(s) selected from the abovegroup B, or (10′) C₃₋₈ cycloalkyl C₁₋₆ alkyl optionally substituted by 1to 5 substituent(s) selected from the above group B, (k)—(CH₂)_(t)—O—(CH₂)_(p)—COR^(a21) wherein R^(a21) is amino, C₁₋₆alkylamino or heterocyclic group optionally substituted by 1 to 5substituent(s) selected from the above group B, and p is 0 or an integerof 1 to 6, (l) —(CH₂)_(t)—NR^(a22)R^(a23) wherein R^(a22) and R^(a23)are each independently (1′) hydrogen atom, (2′) optionally substitutedC₁₋₆ alkyl (as defined above), (3′) C₆₋₁₄ aryl optionally substituted by1 to 5 substituent(s) selected from the above group B, (4′) C₆₋₁₄ arylC₁₋₆ alkyl optionally substituted by 1 to 5 substituent(s) selected fromthe above group B, (5′) heterocycle C₁₋₆ alkyl optionally substituted by1 to 5 substituent(s) selected from the above group B or (6′)heterocyclic group optionally substituted by 1 to 5 substituent(s)selected from the above group B, (m) —(CH₂)_(t)—NR^(a29)CO—R^(a24)wherein R^(a29) is hydrogen atom, C₁₋₆ alkyl or C₁₋₆ alkanoyl, andR^(a14) is (1′) amino, (2′) C₁₋₆ alkylamino, (3′) optionally substitutedC₁₋₆ alkyl (as defined above), (4′) C₆₋₁₄ aryl optionally substituted by1 to 5 substituent(s) selected from the above group B, (5′) heterocyclicgroup optionally substituted by 1 to 5 substituent(s) selected from theabove group B, or (6′) heterocycle C₁₋₆ alkyl optionally substituted by1 to 5 substituent(s) selected from the above group B, (n)—(CH₂)_(t)—NR^(a29)SO₂—R^(a25) wherein R^(a29) is as defined above, andR^(a25) is hydrogen atom, optionally substituted C₁₋₆ alkyl (as definedabove), C₆₋₁₄ aryl optionally substituted by 1 to 5 substituent(s)selected from the above group B or heterocyclic group optionallysubstituted by 1 to 5 substituent(s) selected from the above group B,(o) —(CH₂)_(t)—S(O)_(q)—R^(a25) wherein R^(a25) is as defined above, andq is 0, 1 or 2, (p) —(CH₂)_(t)—SO₂—NHR^(a26) wherein R^(a26) is hydrogenatom, optionally substituted C₁₋₆ alkyl (as defined above), C₆₋₁₄ aryloptionally substituted by 1 to 5 substituent(s) selected from the abovegroup B or heterocyclic group optionally substituted by 1 to 5substituent(s) selected from the above group B, and (q) heterocyclicgroup having 1 to 4 heteroatom(s) selected from an oxygen atom, anitrogen atom and a sulfur atom, w is an integer of 1 to 3, and Y is (1)a single bond, (2) C₁₋₆ alkylene, (3) C₂₋₆ alkenylene, (4)—(CH₂)_(m)—O—(CH₂)_(n)—, (hereinafter m and n are each independently 0or an integer of 1 to 6), (5) —CO—, (6) —CO₂—(CH₂)_(n)—, (7)—CONH—(CH₂)_(n)—NH—, (8) —NHCO₂—, (9) —NHCONH—, (10) —O—(CH₂)_(n)—CO—,(11) —O—(CH₂)_(n)—O—, (12) —SO₂—, (13) —(CH₂)_(m)—NR^(a12)—(CH₂)_(n)—wherein R^(a12) is (1′) hydrogen atom, (2′) optionally substituted C₁₋₆alkyl (as defined above), (3′) C₆₋₁₄ aryl C₁₋₆ alkyl optionallysubstituted by 1 to 5 substituent(s) selected from the above group B,(4′) C₆₋₁₄ aryl optionally substituted by 1 to 5 substituent(s) selectedfrom the above group B, (5′) —COR^(b5)  wherein R^(b5) is hydrogen atom,optionally substituted C₁₋₆ alkyl (as defined above),  C₆₋₁₄ aryloptionally substituted by 1 to 5 substituent(s) selected from the abovegroup B or C₆₋₁₄ aryl C₁₋₆ alkyl optionally substituted by 1 to 5substituent(s) selected from the above group B, (6′) —COOR^(b5) (R^(b5)is as defined above) or (7′) —SO₂R^(b5) (R^(b5) is as defined above),(14) —NR^(a12)CO— (R^(a12) is as defined above), (15)—CONR^(a13)—(CH₂)_(n)— wherein R^(a13) is hydrogen atom, optionallysubstituted C₁₋₆ alkyl (as defined above) or C₆₋₁₄ aryl C₁₋₆ alkyloptionally substituted by 1 to 5 substituent(s) selected from the abovegroup B, (16) —CONH—CHR^(a14) wherein R^(a14) is C₆₋₁₄ aryl optionallysubstituted by 1 to 5 substituent(s) selected from the above group B,(17) —O—(CH₂)_(m)—CR^(a15)R^(a16)—(CH₂)_(n)— wherein R^(a15) and R^(a16)are each independently (1′) hydrogen atom, (2′) carboxyl, (3′) C₁₋₆alkyl, (4′) —OR^(b6) wherein R^(b6) is C₁₋₆ alkyl or C₆₋₁₄ aryl C₁₋₆alkyl, or (5′) —NHR^(b7) wherein R^(b7) is hydrogen atom, C₁₋₆ alkyl,C₁₋₆ alkanoyl or C₆₋₁₄ aryl C₁₋₆ alkyloxycarbonyl, or R^(a15) isoptionally

 wherein n′, ring B′, Z′ and w′ are the same as the above-mentioned n,ring B, Z and w, respectively, and may be the same as or different fromthe respective counterparts, (18) —(CH₂)_(n)—NR^(a12)—CHR^(a15)—(R^(a12)and R^(a15) are each as defined above), (19) —NR^(a17)SO₂ whereinR^(a17) is hydrogen atom or C₁₋₆ alkyl, (20)—S(O)_(e)—(CH₂)_(m)—CR^(a15)R^(a16)—(CH₂)_(n)— (e is 0, 1 or 2, R^(a15)and R^(a16) are each as defined above), or (21)—(CH₂)_(m)—CR^(a15)R^(a16)—(CH₂)_(n)—(R^(a15) and R^(a16) are each asdefined above), or a pharmaceutically acceptable salt thereof. 30.-63.(canceled)
 64. A hepatitis C virus polymerase inhibitor comprising afused ring compound of claim 1, or a pharmaceutically acceptable saltthereof, and a pharmaceutically acceptable carrier.
 65. Ananti-hepatitis C virus agent comprising a fused ring compound of claim1, or a pharmaceutically acceptable salt thereof, and a pharmaceuticallyacceptable carrier.
 66. (canceled)
 67. An anti-hepatitis C virus agentcomprising (a) the anti-hepatitis C virus agent of claim 65 and (b) atleast one agent selected from the group consisting of a differentantiviral agent, an antiinflammatory agent and an immunostimulant. 68.An anti-hepatitis C virus agent comprising (a) the anti-hepatitis Cvirus agent of claim 65 and (b) interferon.
 69. A therapeutic agent forhepatitis C comprising (a) the hepatitis C virus polymerase inhibitor ofclaim 64 and (b) at least one agent selected from the group consistingof a different antiviral agent, an antiinflammatory agent and animmunostimulant.
 70. A therapeutic agent for hepatitis C comprising (a)the hepatitis C virus polymerase inhibitor of claim 64 and (b)interferon.
 71. A benzimidazole compound of the folllowing formula [III]

wherein R^(a36) is hydrogen atom or carboxyl-protecting group, R^(a37)is cyclopentyl or cyclohexyl, and R^(a38) is hydrogen atom or fluorineatom, or a salt thereof.
 72. A thiazole compound selected from the groupconsisting of 4-(4-fluorophenyl)-5-hydroxymethyl-2-methylthiazole and4-(4-fluorophenyl)-5-chloromethyl-2-methylthiazole, or apharmaceutically acceptable salt thereof.
 73. A biphenyl compoundselected from the group consisting of1-(4′-chloro-2-hydroxymethyl-biphenyl-4-yl)-2-pyrrolidinone and1-(4′-chloro-2-chloromethyl-biphenyl-4-yl)-2-pyrrolidinone, or apharmaceutically acceptable salt thereof.
 74. A pharmaceuticalcomposition comprising (a) a fused ring compound of the formula [I] ofclaim 1 or a pharmaceutically acceptable salt thereof and (b) at leastone agent selected from the group consisting of an antiviral agent otherthan the compound of claim 1, an antiinflammatory agent and animmunostimulant.
 75. A pharmaceutical composition comprising (a) a fusedring compound of the formula [I] of claim 1 or a pharmaceuticallyacceptable salt thereof and (b) interferon.
 76. A method for treatinghepatitis C, which comprises administering an effective amount of afused ring compound of the formula [I] of claim 1 or a pharmaceuticallyacceptable salt thereof.
 77. The method of claim 76, further comprisingadministering an effective amount of at least one agent selected fromthe group consisting of an antiviral agent other than the compound ofclaim 1, an antiinflammatory agent and an immunostimulant.
 78. Themethod of claim 76, further comprising administering an effective amountof interferon.
 79. A method for inhibiting hepatitis C virus polymerase,which comprises administering an effective amount of a fused ringcompound of the formula [I] of claim 1 or a pharmaceutically acceptablesalt thereof.
 80. The method of claim 79, further comprisingadministering an effective amount of at least one agent selected fromthe group consisting of an antiviral agent other than the compound ofclaim 1, an antiinflammatory agent and an immunostimulant.
 81. Themethod of claim 79, further comprising administering an effective amountof interferon. 82.1-Cyclohexyl-2-(3-furanyl)-1H-benzimidazole-5-carboxylic acid.